1.

Segall et al (2008) reported that protein-calorie malnutrition is a common complication

and an important predictive factor for mortality in patients with end-stage renal disease
on maintenance dialysis. Therefore, nutritional status needs to be regularly assessed in
these patients by using several methods. If malnutrition is diagnosed, its causes should be
thoroughly searched for and properly treated. Their study aimed at evaluating the
nutritional status and the possible risk factors for malnutrition in 149 (82 men)
hemodialysis patients by anthropometry, biochemical tests and bioelectrical impedance
analysis (BIA). The patients' height (H), post-dialysis body weight (BW), mid-arm
circumference (MAC), tricipital skin-fold thickness (TST) were measured and a 3-
category subjective global assessment (SGA) was performed. Body mass index (BMI),
mid-arm muscle circumference (MAMC), corrected mid-arm muscle area (cMAMA) and
anthropometry-estimated percent body muscle mass (% AMM) were calculated from the
above measurements by using specific equations. Biochemical tests included protein
equivalent of nitrogen appearance (nPNA), and predialysis serum albumin, creatinine,
total cholesterol, bicarbonate, and hemoglobin (Hb) levels. They used BIA to estimate
body composition - i.e. percent body fat (% BBF), fat-free mass (% FFM), body cell
mass (% BCM), extracellular mass (% ECM), muscle mass (% BMM)--and the phase
angle (PhA). T-test was used to make comparisons and Pearson coefficient to analyze the
correlations. P < 0.05 was considered statistically significant. Their results showed that
male patients had a higher mean muscle mass--as estimated by serum creatinine (9.8 s 8.3
mg/dl; P < 0.0001) and by % BMM (41.7% vs 34.7%)--and a lower fat mass--as
estimated by TST (0.95 cm vs 1.2 cm; P = 0.016) and by % FAT (16.7% vs 31.3%; P <
0.0001) than the female patients. Age was found to be positively correlated with BMI (P
= 0.001), but inversely correlated with % BCM (P = 0.013) and with % AMM (P =
0.003). Patients with diabetes had lower % BCM than those without diabetes (32.9 vs
35.9%; P = 0.041). The presence of heart failure was associated with significantly
reduced MAMC (22.0 vs 23.6 cm2; P = 0.045), % AMM (28.5 vs 32.1; P = 0.021), %
BCM (33.0 vs 36.1% ; P = 0.034), BMM/H2 (8.6 vs 9.4 kg/m2; P = 0.013), nPNA (1.17
vs 1.34 g/kg-d ; P = 0.047), serum albumin (39.7 vs 42.4 g/l; P = 0.010), serum creatinine
(8.1 vs 9.4 mg/dl; P = 0.008) and Hb (10.5 vs 11.2 g/dl; P = 0.017). The serum Hb level
was positively correlated with BMI (P = 0.005), BMM/H2 (P = 0.009), serum albumin (P
= 0.002) and serum creatinine (P = 0.011). Also, patients with category B-SGA were
older (63.7 vs 50.1 y.o.; P < 0.0001) and had more heart failure (42% vs 13%; P = 0.013)
than those with category A-SGA. Their study concluded that in hemodialysis patients,
advancing age, diabetes, heart failure and decreasing Hb levels are associated with worse
nutritional status, as estimated by anthropometry, biochemical markers and BIA. Whether
treatment of comorbidities such as heart disease and anemia may improve nutritional
status in these patients is an important issue that deserves further research.

2. Hallan et al. (2006) investigated associations between obesity, smoking, and physical
inactivity and chronic kidney disease (CKD) in the general population and whether risk
for CKD was restricted to men. They carried out a cross-sectional health survey of the
entire adult population of Nord-Trondelag County, Norway, 1995 to 1997, with a 70.6%
participation rate. Glomerular filtration rate (GFR) was estimated in all subjects 20 years
and older from calibrated serum creatinine levels by using the simplified Modification of
Diet in Renal Disease Study formula, and CKD cases are defined as those with a GFR

1
less than 45 mL/min/1.73 m2 (<0.75 mL/s). They included a total of 30,485 men and
34,708 women, and prevalences of GFR less than 45 mL/min/1.73 m2 (<0.75 mL/s) were
0.8% and 1.1%, respectively. Age- and sex-adjusted logistic regression analyses showed
dose-response relations for body mass index, smoking history, and physical activity.
Relative risks were 1.77 (95% confidence interval [CI], 1.47 to 2.14) for obesity (body
mass index ≥ 30 kg/m2), 1.52 (95% CI, 1.13 to 2.06) for smoking (>25 pack-years), and
2.14 (95% CI, 1.39 to 3.30) for physical inactivity (no or some physical activity in leisure
time). For subjects with all these risk factors, relative risk was 5.10 (95% CI, 2.36 to
11.01). Their results remained significant after adjusting for other known risk factors. No
biological interactions between sex and obesity, smoking, or physical activity were
found. They concluded that obesity, smoking, and physical inactivity were associated
significantly with CKD. Men were not more susceptible to these risk factors than women.

3. Hsu et al. (2006) described that although interest in the relationship between obesity
and kidney disease is increasing, few epidemiologic studies have examined whether
excess weight is an independent risk factor for end-stage renal disease (ESRD).Therefore
they determined the association between increased body mass index (BMI) and risk for
ESRD. They carried out a historical (nonconcurrent) cohort study in a large integrated
health care delivery system in northern California by selecting 320,252 adult members
of Kaiser Permanente who volunteered for screening health checkups between 1964 and
1985 and who had height and weight measured. The authors ascertained ESRD cases by
matching data with the U.S. Renal Data System registry through 2000.Results obtained
were a total of 1471 cases of ESRD occurred during 8,347,955 person-years of follow-up.
Higher BMI was a risk factor for ESRD in multivariable models that adjusted for age,
sex, race, education level, smoking status, history of myocardial infarction, serum
cholesterol level, urinalysis proteinuria, urinalysis hematuria, and serum creatinine level.
Compared with persons who had normal weight (BMI, 18.5 to 24.9 kg/m2), the adjusted
relative risk for ESRD was 1.87 (95% CI, 1.64 to 2.14) for those who were overweight
(BMI, 25.0 to 29.9 kg/m2), 3.57 (CI, 3.05 to 4.18) for those with class I obesity (BMI,
30.0 to 34.9 kg/m2), 6.12 (CI, 4.97 to 7.54) for those with class II obesity (BMI, 35.0 to
39.9 kg/m2), and 7.07 (CI, 5.37 to 9.31) for those with extreme obesity (BMI > or = 40
kg/m2). Higher baseline BMI remained an independent predictor for ESRD after
additional adjustments for baseline blood pressure level and presence or absence of
diabetes mellitus. Primary analyses based on single measurements of exposures were
limitation of their study. They concluded high BMI is a common, strong, and potentially
modifiable risk factor for ESRD.

4. Hsu et al. (2005) reported that many cases of end-stage renal disease (ESRD) are
ascribed to hypertension. However, because renal disease itself can raise blood pressure,
some investigators argue that ESRD seen in patients with hypertension is due to
underlying primary renal disease. Previous cohort studies of the relationship between
blood pressure and ESRD did not uniformly screen out baseline kidney disease. They
conducted a historical cohort study among members of Kaiser Permanente of Northern
California, a large integrated health care delivery system. The ESRD cases were
ascertained by matching with the US Renal Data System registry. A total of 316 675
adult Kaiser Members participated in the Multiphasic Health Checkups from 1964 to

2
1985. All subjects had estimated glomerular filtration rates of 60 mL /min per 1.73 m (2)
or higher and negative dipstick urinalysis results for proteinuria or hematuria. During 8
210 431 person-years of follow-up, 1149 cases of ESRD occurred. Compared with
subjects with a blood pressure less than 120/80 mm Hg, the adjusted relative risks for
developing ESRD were 1.62 (95% confidence interval [CI], 1.27-2.07) for blood
pressures of 120 to 129/80 to 84 mm Hg, 1.98 (95% CI, 1.55-2.52) for blood pressures of
130 to 139/85 to 89 mm Hg, 2.59 (95% CI, 2.07-3.25) for blood pressures of 140 to
159/90 to 99 mm Hg, 3.86 (95% CI, 3.00-4.96) for blood pressures of 160 to 179/100 to
109 mm Hg, 3.88 (95% CI, 2.82-5.34) for blood pressures of 180 to 209/110 to 119 mm
Hg, and 4.25 (95% CI, 2.63-6.86) for blood pressures of 210/120 mm Hg or higher.
Similar associations between blood pressure level and ESRD risk were seen in all
subgroup analyses. They summed up that even relatively modest elevation in blood
pressure is an independent risk factor for ESRD. The observed relationship does not
appear to be due to confounding by clinically evident baseline kidney disease

5. Kumagai (2007) reported that protein energy malnutrition (PEM) frequently appears in
hemodialysis (HD) patients, and it has been established as a risk factor for morbidity and
mortality. Recent studies have shown that inflammation might be a key mediator between
PEM and cardiovascular events. On the other hand, it remains unknown whether over-
nutrition has an implication as a risk factor for cardiovascular diseases and mortality.
Although many studies have indicated that obesity seemed not to be directly associated
with mortality, metabolic abnormalities including hypertriglyceridemia, a low level of
high-density lipoprotein cholesterol, glucose intolerance and visceral fat accumulation are
common in HD patients with over-nutrition. Furthermore, the plasma adiponectin
concentration has been reported to show an inverse correlation with the visceral fat mass,
and low plasma adiponectin was associated with a high susceptibility to cardiovascular
events and mortality in HD patients. These results suggest that nutritional therapy for HD
patients may be necessary to consider in patients with either PEM or over-nutrition.

6. Hirachan et al. (2008) reported that in contrast to epidemiological data from the
general population, maintenance hemodialysis (MHD) patients with a naturally small
body size experience an increased mortality rate compared to their larger fellow patients.
Since body mass index is a poor surrogate of body composition, attempts were made to
delineate muscle, fat and visceral organ mass in MHD patients. Several lines of evidence
indicate that (a) increased fat and muscle mass exerts protective effects, (b) some markers
of inflammation may be increased with fat mass, and (c) a high visceral mass per body
weight is associated with a reduced survival time. The reasons for the positive effects of
fat and muscle mass on survival are not clear. A novel hypothesis predicts lower uremic
toxin concentrations in larger subjects. This is based on the observation that both in
healthy subjects and in dialysis patients, visceral organ mass are inversely related to body
mass. Since visceral organs are the most prominent source of uremic toxins, large
patients may have a lower toxin production rate per unit of body mass. Moreover, large
patients have a greater volume of distribution (total body water, fat mass) resulting in
lower toxin concentrations. Future studies should aim to tackle the Janus-like duality of
obesity by a system biology approach.

3
7. Mafra et al. (2007) studied the impact of serum albumin and body-mass index on
survival in hemodialysis patients. A low body mass index (BMI) and serum albumin are
associated with increased risk of mortality in patients with chronic kidney disease (CKD).
The purpose of their study was to evaluate BMI and serum albumin as predictors of all-
cause and cardiovascular (CV) mortality in hemodialysed (HD) patients. They described
the results of a five-year retrospective observational study with 187 HD patients (54.9 +/-
15.6 years old, 54% men, and 46% suffering from diabetes) from RenalCor Clinic in Rio
de Janeiro, Brazil. The influence of serum albumin levels and BMI (determined every
three months) over all-cause mortality was examined using a Cox model, while the
influence of the same factors over CV mortality among all-cause mortality was modeled
through a logistic regression. During the five years, 26.7% of the patients died, 62% of
which due to CV disease (CVD). Analysis by the Cox model showed that low serum
albumin and low BMI were significant predictors of mortality. Patients with higher BMI
had a lower hazard of death for all-cause mortality (hazard ratio [HR] = 0.92; P ( ) =
0.035) and a 1 g/l increase in serum albumin was associated with significantly lower
hazard of death (hazard ratio = 0.9679; P < 0.001). The highest BMI value (>30 kg/m (2))
was significantly associated with an increase of odds of CV mortality (odds ratio = 1.22,
P = 0.03). They confirmed here in a Brazilian cohort of hemodialysis patients that both
low BMI (<19 kg/m (2)) and hypoalbuminemia are strong predictors of death.

8. Akgul et al. (2007) reported that the possible interactions between inflammatory and
nutritional markers and their impact on recombinant human erythropoietin (rHuEPO)
hyporesponsiveness are not well understood. They investigated the role of nutritional
status in rHuEPO requirement in maintenance hemodialysis (MHD) patients without
evidence of inflammation. In a cross-sectional study they included 88 MHD patients.
They analyzed the associations between required rHuEPO dose and malnutrition-
inflammation score (MIS) and several laboratory values known to be related to nutrition
and/or inflammation. Anthropometric measures including body mass index, triceps
skinfold thickness, and midarm circumferences were also measured. Twenty-three
patients with serum C-reactive protein levels >10 mg/L were excluded from the analysis.
The remaining 65 patients (male/female, 41/24; age 49.1+/-11.4 years; dialysis duration
99.7+/-63.0 months) were studied. These patients had moderate malnutrition and the
average MIS was 7.4 (range 3-17). The average weekly dose of administered rHuEPO
was 69.1+/-63.1 U/kg. Malnutrition-inflammation score had a positive correlation with
the serum concentration of tumor necrosis factor-alpha, whereas it had a negative
correlation with anthropometric measures, total iron-binding capacity, prealbumin,
phosphorus, creatinine, and triglyceride. According to Pearson's correlation analysis,
significant relationships of increased MIS with increased required rHuEPO dose and
rHuEPO responsiveness index (EPO divided by hematocrit) were observed (p=0.008, r=-
0.326; p=0.017, r=-0.306, respectively). They concluded that recombinant human
erythropoietin dose requirement is correlated with MIS and adverse nutritional status in
MHD patients without evidence of inflammation. Further research should focus on
reversing the undergoing microinflammation for a better outcome in dialysis patients.

9. Van et al. (2010) revealed that diabetic nephropathy is now the most common cause of
end-stage renal failure in many countries of the world. Despite increasing implementation

4
of preventive treatment, the chance that an individual diabetic patient will reach end-
stage renal failure has been increasing rather than decreasing during recent decades.
Current dietary habits in Netherlands and the rest of the Western world are slowly
shifting from relatively alkalinizing (e.g., potatoes and vegetables) toward more
acidifying (e.g., rice and meat). Moreover, immigrants who consumed traditional diets in
their homelands, usually adapt to Western dietary habits. This phenomenon of diet
acculturation could, for instance, be involved in the up to 40 times higher chance of
development of end-stage renal failure in association with diabetes in South-Asian
immigrants compared with whites, in Western countries. High ingestion of nonvolatile
acids with food increases susceptibility for progression to end-stage renal failure. These
high dietary acid loads lead to compensatory increases in renal acid excretion and
ammoniagenesis. The price paid for maintenance of acid-base homeostasis is renal
tubulointerstitial injury, with subsequent decline in renal function and induction of
hypertension. The tendency for metabolic acidosis that results from the changing dietary
habits could be corrected by a shift toward more alkalinizing food. They hypothesized
that promoting such a shift can prevent the epidemic of end-stage renal failure in
diabetes.

10. Horl. (2010) studied that hypertension is a risk factor for cardiovascular morbidity
and mortality. Hypertension affects the majority of haemodialysis (HD) patients.
However, in the absence of prospective data, accurate assessment of blood pressure (BP)
and the level to which BP should be targeted remain still to be defined. A direct
relationship between volume status and BP as well as between hypervolaemia and
morbidity and mortality in HD patients indicates that normovolaemia is the key
therapeutic target. Dry-weight reduction by additional ultrafiltration (even in the absence
of clinical signs of volume overload) combined with daily dietary salt restriction or
individually lowered dialysate sodium is recommended. Strict volume control allows
marked reduction of antihypertensive drug treatment or makes it even unnecessary. Long,
slow, home HD or frequent, short HD sessions or nocturnal HD also result in reduction of
BP and left ventricular hypertrophy in end-stage renal disease patients. It will be
interesting to see which recommendations will come from a conference sponsored by the
Kidney Disease: Improving Global Outcomes on optimal BP treatment target in relation
to end-organ damage and outcomes in HD patients, on antihypertensive drugs and on
non-pharmacological therapies are to be considered in achieving BP targets in this
population based on a paucity of prospective data.

11. Agarwal. (2010) reported that hypervolemia is associated with increased mortality
among hemodialysis patients. Among chronic hemodialysis patients, 217 hospitalizations
per 1000 patient-years are attributed to congestive heart failure; some are attributable to
unrecognized hypervolemia. Hypervolemia can be detected by relative plasma volume
(RPV) monitoring. The purpose of this study was to examine among 308 patients on
long-term hemodialysis the value of slope of RPV compared with either ultrafiltration
(UF) volume or UF rate index in determining all-cause mortality. RPV slopes were
calculated by least-squares regression. These slopes were related to all-cause mortality in
unadjusted and adjusted Cox proportional hazards models. Over a median follow-up of
30 months (interquartile range: 14 to 54 months) 96 patients (31%) died, yielding a crude

5
mortality rate of 113/1000 patient-years. They found the following: (1) RPV slope
measurements were of prognostic significance (hazard ratio of flatter slopes [>1.39%/h]:
1.72; P=0.01); (2) the UF volume alone was not prognostically informative (hazard ratio
of higher UF volume [>2.7 L of dialysis]: 0.78; P=0.23); (3) the UF rate index alone was
also not prognostically informative (hazard ratio of higher UF rate index [>8.4 mL/kg per
hour]: 0.89; P=0.6); and (4) the prognostic relationship of RPV slope to mortality was
independent of conventional and unconventional cardiovascular risk factors including the
UF volume, UF rate, or UF volume per kilogram of postweight. RPV monitoring yields
information that is prognostically important and independent of several risk factors
including UF volume, aggressiveness of UF, and interdialytic ambulatory blood pressure.
Its use to assess excess volume-related morbidity among chronic hemodialysis patients
should be tested in randomized, controlled trials.

12. Feroze et al. (2010) reviewed that depression and anxiety are among the most
common comorbid illnesses in people with end-stage renal disease (ESRD). Patients with
ESRD face many challenges which increase the likelihood that they will develop
depression or anxiety or worsen these conditions. These include a general feeling of
unwellness; specific symptoms caused by ESRD or the patient's treatment; major
disruptions in lifestyle; the need to comply with treatment regimens, including dialysis
schedules, diet prescription, and water restriction; ancillary treatments and
hospitalizations; and the fear of disability, morbidity, and shortened lifespan. Depression
has been studied extensively in patients on maintenance dialysis, and much effort has
been done to validate the proper screening tools to diagnose depression and to define the
treatment options for patients on maintenance dialysis with depression. Anxiety is less
well studied in this population of patients. Evidence indicates that anxiety is also
common in maintenance dialysis. More attention should be paid to measuring the
incidence and prevalence and developing methods of diagnosis and treatment approaches
for anxiety in patients with ESRD. In this review, they attempted to underscore those
aspects of depression and anxiety that have not been investigated extensively, especially
with regard to anxiety. The interaction between racial/ethnic characteristics of patients on
maintenance dialysis with depression and anxiety needs to be studied more extensively,
in order to assess better approaches to healthcare for these individuals.

13. Noori and Kopple. (2010) studied the effect of diabetes mellitus on protein-energy
wasting and protein wasting in end-stage renal disease. Protein wasting (PW) or protein-
energy wasting (PEW) occurs commonly in patients with diabetes mellitus who have
end-stage renal disease (ESRD) and are undergoing maintenance dialysis (MD) therapy.
Some but not all studies indicated that PW or PEW is more prevalent in diabetic when
compared with nondiabetic MD patients and that diabetic patients commencing
maintenance hemodialysis (MHD) are more likely to lose fat-free, edema-free weight
than are incident nondiabetic MHD patients. The causes of PW and PEW in diabetic MD
patients are probably largely similar to those of nondiabetic MD patients. These causes
include anorexia, reduced food intake, concurrent illnesses particularly when associated
with inflammatory processes, physical or mental debility, removal of nutrients by dialysis
procedure, acidemia, possibly physical deconditioning, and oxidant and carbonyl stress.

6
However, diabetic MD patients are also at greater risk for PW or PEW from
comorbidities related to diabetes per se. These disorders include ischemic vascular
disease, hypertension, gastrointestinal dysfunction, and neuropathy. Metabolic disorders
such as insulin deficiency or resistance to the actions of insulin, and elevated levels of
counterregulatory hormones may also contribute to PW or PEW in diabetic MD patients.
Mechanisms by which these metabolic disorders in diabetic ESRD patients may cause
PW or PEW are discussed.

14. Dukkipati and Kopple. (2009) studied the causes and prevention of protein-energy
wasting in chronic kidney failure. Protein-energy wasting (PEW), defined as reduced
somatic and/or circulating body protein mass, decreased fat mass, and usually reduced
protein and energy intake, has a prevalence that is variously estimated to be 18% to 75%
in maintenance hemodialysis and chronic peritoneal dialysis patients. PEW is associated
with increased morbidity and mortality and often is preventable or treatable. Thus, it has
been argued that maintenance hemodialysis and chronic peritoneal dialysis patients
should be monitored routinely for PEW and treated for this condition, when it occurs. A
trend toward PEW can emerge in early stage 3 chronic kidney disease with an increasing
risk toward the development and worsening of PEW as chronic kidney disease
progresses. A main cause of PEW is inflammation, which may occur with or without
clinically evident illness and can be associated with the most severe forms of PEW.
Another major cause of PEW is decreased nutrient intake relative to the patient's
nutritional needs, and may be caused by anorexia, which may be engendered by uremic
toxicity, emotional depression, medications, or inflammatory disorders. Nonanorexic
causes of reduced nutrient intake include inadequate finances to purchase or prepare
foods; medical or surgical illnesses that impair the person's ability to ingest, digest,
assimilate, or process the nutrients; impaired cognitive function; other mental or physical
disabilities; and loss of dentures. Losses of nutrients during dialysis treatments or in urine
(e.g. the nephrotic syndrome), acidemia, and hormonal disorders can contribute to the
development of PEW. Early initiation and adequate doses of renal replacement therapy,
rapid treatment of reversible inflammatory processes, ensuring an adequate nutrient
intake, and prevention of acidemia may be used to prevent and treat PEW.

15. Szczech et al. (2010) studied acute kidney injury and cardiovascular outcomes in
acute severe hypertension. They reported that little is known about the association of
kidney dysfunction and outcome in acute severe hypertension so their study aimed to
measure the association between baseline chronic kidney disease (estimated glomerular
filtration rate), acute kidney injury (AKI, decrease in estimated glomerular filtration rate
> or =25% from baseline) and outcome in patients hospitalized with acute severe
hypertension. The Studying the Treatment of Acute Hypertension (STAT) registry
enrolled patients with acute severe hypertension, defined as > or =1 blood pressure
measurement >180 mm Hg systolic and/or >110 mm Hg diastolic and treated with
intravenous antihypertensive therapy. Data were compared across groups categorized by
admission estimated glomerular filtration rate and AKI during admission. On admission,
79% of the cohort (n=1566) had at least mild chronic kidney disease (estimated
glomerular filtration rate <60 mL/min in 46%, <30 mL/min in 22%). Chronic kidney
disease patients were more likely to develop heart failure (P<0.0001), non-ST-elevation

7
myocardial infarction (P=0.003), and AKI (P<0.007). AKI patients were at greater risk of
heart failure and cardiac arrest (P< or =0.0001 for both). Subjects with AKI experienced
higher mortality at 90 days (P=0.003). Any acute loss of estimated glomerular filtration
rate during hospitalization was independently associated with an increased risk of death
(odds ratio, 1.05; P=0.03 per 10-mL/min decline). Other independent predictors of
mortality included increasing age (P<0.0001), male gender (P=0.016), white versus black
race (P=0.003), and worse baseline kidney function (P=0.003).They summed up that
chronic kidney disease is a common comorbidity among patients admitted with acute
severe hypertension, and AKI is a frequent form of acute target organ dysfunction,
particularly in those with baseline chronic kidney disease. Any degree of AKI is
associated with a greater risk of morbidity and mortality.

16. Schmid and Schiff. (2010) revealed that chronic kidney disease (CKD) is a
widespread health problem in the world and anaemia of renal origin is a common
problem. Anaemia associated with CKD covers significant risk for faster progression of
chronic renal failure, decreased quality of life, and clinical manifestation of
cardiovascular disease. The mainstay of anaemia treatment secondary to end-stage renal
disease (ESRD) has become erythropoiesis stimulating agents (ESAs). More than 90 %
of ESRD patients maintained on dialysis respond to traditional recombinant human
erythropoietin (rHU EPO) or to EPO analogues, also called "biosimilars". Iron deficiency
often co-exists in dialysis patients and must be evaluated and treated to reduce ESA
requirements. Partial, but not complete correction of renal anaemia is associated with
improved outcomes in patients with CKD. The use of ESAs does carry risks such as
hypertension, pure red cell aplasia, or cancer, and these agents need to be used
judiciously.

17. Besarab and Coyne. (2010) reported that iron deficiency is prevalent in patients with
chronic kidney disease (CKD), and use of oral and intravenous iron in patients with CKD
who do not require dialysis might obviate or delay the need for treatment with
eythropoiesis-stimulating agents (ESAs). Patients on hemodialysis have lower intestinal
iron absorption, greater iron losses, and require greater iron turnover to maintain the
ESA-driven red cell mass than do healthy individuals. In these patients, intravenous iron
reduces ESA dose requirements and increases the likelihood of maintaining levels of
hemoglobin within the desired range. Oral iron is inferior to intravenous iron in patients
on hemodialysis, in part because elevated serum levels of hepcidin prevent intestinal
absorption of iron. Increased levels of hepcidin also impair the normal recycling of iron
through the reticuloendothelial system. Levels of serum ferritin and transferrin saturation
below 450 pmol/l and 20%, respectively are indicative of iron deficiency, but values
above the normal range lack diagnostic value in patients with CKD on dialysis. The
availability of various iron preparations and new developments in delivering iron should
enable adequate provision of iron to patients with CKD. This Review examined the
efficacy, safety and use of iron supplementation therapy for the treatment of anemia in
patients with CKD

18. Mohamed. (2010) reported that hepatitis C virus (HCV) has been a significant
problem in hemodialysis (HD) patients. In general, it carries significant morbidity

8
including liver cirrhosis, liver cell failure and hepatoma. Their study was conducted on
36 seronegative HD patients. All patients were managed with strict application of
infection control guidelines as well as isolation of HCV-positive patients. None of the
patients received any blood transfusions and were managed with iron and erythropoietin.
After five years of follow-up, they found that the incidence of HCV seroconversion was
zero. Their study further suggests that following infection control guidelines, isolation of
seropositive patients and minimizing blood transfusions can help in prevention of HCV
transmission among HD patients.

19. Asci et al. (2010) studied the link between bone and coronary calcifications in CKD-5
patients on haemodialysis. Vascular calcifications are frequent in Stage 5 chronic kidney
disease (CKD-5) patients receiving haemodialysis. Their study was designed to evaluate
the associations between bone turnover/volume and coronary artery calcifications (CAC).
In 207 CKD-5 patients, bone biopsies, multislice computed tomography of the coronary
arteries and blood drawings for relevant biochemical parameters were done. The large
number of CKD-5 patients enrolled allowed separate evaluation of patients with CAC
versus patients without CAC and adjustment for traditional and non-traditional risk
factors for CAC.When all patients were analysed, associations were found between CAC
and bone turnover, bone volume, age, gender and dialysis vintage. When only patients
with CAC were included, there was a U-shaped relationship between CAC and bone
turnover, whilst the association with bone volume was lost. In these patients, the
relationship of CAC with age, gender and dialysis vintage remained. Beyond the non-
modifiable risk factors of age, gender and dialysis vintage, these data showed that bone
abnormalities of renal osteodystrophy amenable to treatment.

20. Lindley. (2009) reported that a low salt diet is beneficial for the whole population but
has particular advantages for hemodialyis patients because of the role of salt restriction in
the management of hypertension and interdialytic weight gain (IDWG). Education on
dietary salt intake based on general healthy eating guidelines, such as the “DASH-
sodium” diet, should be provided for staff, families, and carers as well as patients. Anuric
hemodialysis patients will need to take in approximately 1 l of water for every 8 g salt
consumed. Patients who restrict salt intake to <6 g/day, and drink only when thirsty,
should gain no more than 0.8 kg/day. Those with significantly greater weight gains, but
predialysis serum sodium close to or higher than the dialysate sodium, need further
review of their salt intake. Attempts to restrict fluid intake in these patients will be futile.
Patients with high interdialytic weight gain (IDWG) and low predialysis sodium should
be assessed for other reasons for fluid intake, such as high blood glucose or social
drinking. For patients with poor tolerance of fluid removal during dialysis, and those who
are hypertensive in the absence of fluid overload, a salt intake 5 g/day or less may be
required. Dietary advice for these patients should be customized to ensure that they do
not become malnourished.

21. Aoyagi et al. (2001) described that body mass index (BMI) is used as a reference for
weight control programs in the general population and in morbidity and mortality studies
in diabetes patients. However, the implications of BMI in chronic hemodialysis patients
is unclear. They studied the BMI of chronic hemodialysis patients, focusing on problems

9
encountered during outpatient hemodialysis therapy and on 2-year mortality. Outpatients
with chronic hemodialysis (n = 258; 144 men, 114 women) were divided into four
groups: (I) patients with stable hemodialysis; (ii) patients with marked hypotension
requiring catecholamine infusion during hemodialysis; (iii) patients with excessive
interdialysis weight gain requiring occasional additional hemodialysis; and (iv) patients
with troublesome hemodialysis due to other causes. The statistical differences between
the average BMI among these groups were evaluated, and were subdivided into sex, age
and the duration of hemodialysis history. The 2-year mortality rates of these patients were
also studied according to their BMI. In patients under 60 years of age, those with
excessive interdialysis weight gain had statistically larger BMI (23.2; n = 35) compared
to patients with good hemodialysis control (20.1; n = 178), regardless of gender and
hemodialysis history. The mortality rate was at a minimum at approximately 20 BMI in
patients under 60 years of age. However, lower BMI was associated with a greater
mortality rate in patients 60 years or over. For chronic hemodialysis patients, the BMI
associated with stable hemodialysis and minimum mortality is approximately 20, in those
under 60 years of age. The BMI of aged hemodialysis patients should be considered
separately in morbidity and mortality studies.

22. Pifer et al. (2002) revealed that nutritional status is strongly associated with outcomes
among hemodialysis patients. They analyzed the independent predictive value of several
readily measured nutritional indicators, including a modified subjective global
assessment (mSGA), body mass index (BMI), serum albumin, serum creatinine,
normalized protein catabolic rate (nPCR), serum bicarbonate, lymphocyte count, and
neutrophil count, using baseline and six-month follow-up measurements. Their study
sample consisted of 7719 U.S. adult hemodialysis patients enrolled in the international
Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective observational
study that includes a random sample of hemodialysis patients from 145 dialysis facilities
in the United States. Cox regression was used to estimate the relative risk of mortality
associated with differences in measurements at baseline and six months later. Each
analysis was adjusted for age, race, sex, and 15 summary comorbid conditions. The
results showed lower baseline measurements of mSGA, BMI, serum albumin, serum
creatinine, and lymphocyte count were independently associated with significantly higher
risk of mortality. During six-month follow-up, decreases in BMI, serum albumin, and
serum creatinine were also associated with significantly higher mortality risk. The risk of
mortality increased with higher baseline and six-month increases in neutrophil count.
Their study confirmed that several readily-measured nutritional indicators predict
mortality among hemodialysis patients and those changes in indicator values over six
months provide additional important prognostic information. Interventions that modify
these indicators of nutritional status may have an important impact on the survival of
hemodialysis patient

23. Mutsert et al. (2007) revealed that the association of body mass index (BMI) with
mortality in hemodialysis patients has been found to be reversed in comparison with the
general population. They examined the association of BMI with mortality in the
hemodialysis population and the general population when age and time of follow-up were
made strictly comparable. Hemodialysis patients who were aged 50 to 75 yr at the start of

10
follow-up were selected from the Netherlands Cooperative Study on the Adequacy of
Dialysis-2 (NECOSAD), a prospective cohort study in incident dialysis patients in the
Netherlands (n = 722; age 66 ± 7 yr; BMI 25.3 ± 4.5 kg/m2), and compared with adults
who were aged 50 to 75 yr and included in the Hoorn Study, a population-based
prospective cohort study in the same country (n = 2436; age 62 ± 7 yr; BMI 26.5 ± 3.6
kg/m2). In both populations, 2- and 7-yr standardized mortality rates were calculated for
categories of BMI. Adjusted hazard ratios (HR) of BMI categories were calculated with a
BMI of 22.5 to 25 kg/m2 as the reference category within each population. In 7 yr of
follow-up, standardized mortality rates were approximately 10 times higher in the
hemodialysis population than those in the general population. Compared with the
reference category, the HR of BMI <18.5 kg/m2 was 2.0 (95% confidence interval [CI]
1.2 to 3.4) in the hemodialysis population and 2.3 (95% CI 0.7 to 7.5) in the general
population. Obesity (BMI =30 kg/m2) was associated with a HR of 1.2 (95% CI 0.8 to
1.7) in the hemodialysis population and 1.3 (95% CI 0.9 to 2.0) in the general population.
In their conclusion, a hemodialysis population and a general population with comparable
age and equal duration of follow-up showed similar mortality risk patterns associated with
BMI. This suggests that there is no reverse epidemiology of BMI and mortality in
hemodialysis patients. The clinical implication of this study is that to improve survival in
the hemodialysis population, more attention should be paid to patients who are
underweight instead of overweight.

24. Chang et al. (2007) studied the effects of folic acid and vitamin B complex on serum
C-reactive protein and albumin levels in stable hemodialysis patients. Folic acid and
vitamin B complex administration in uremic patients has been reported to lower plasma
total homocysteine (tHcy) levels, but whether or not this has a beneficial effect on the
inflammatory state is not clear. They conducted a randomized open labeled study to
determine the effects of folic acid (5mg daily) and vitamin B complex administration on
plasma tHcy levels as well as inflammatory (serum high-sensitivity C reactive protein,
hs-CRP) and nutritional (serum albumin) markers in patients on maintenance
hemodialysis. Treatment was given for 3 consecutive months to 61 patients on
maintenance hemodialysis. Another 60 patients, all age-, sex-, hemodialysis duration-
matched served as control group. After 3 months, levels of plasma tHcy and serum hs-
CRP, Cr, and nPCR were significantly decreased while levels of serum albumin, vitamin
B [subscript] 12, folate, and BW were significantly increased. The dialytic dose (KT/V)
and dietary intake remained unchanged. However, correlations between the magnitude of
reduction of tHcy & hs-CRP, tHcy & Cr, and Cr & nPCR were statistically significant.
This study confirms that folic acid and vitamin B complex co-administration effectively
lowers tHcy and hs-CRP levels and increases albumin levels in stable hemodialysis
subjects, underscoring their potential benefit to attenuate the state of inflammation and
possibly improve the nutritional status in patients on hemodialysis.

25. Hosokawa and Yoshida. (1994) studied the effects of intravenous erythropoietin on
trace elements and quality of life in chronic hemodialysis patients. The effects of
intravenous erythropoietin on trace elements and quality of life were studied in 30
patients (mean age 51.6 yr) undergoing chronic hemodialysis whose hematocrit levels
had been maintained at 30-50% for 2 yr with the drug. Erythropoietin therapy

11
significantly improved the protein nutritional status, as well as serum zinc, nickel, and
manganese levels; concentrations of zinc ion, nickel ion, and manganese ion in serum
were significantly elevated. Objective and subjective quality of life showed significant
improvement with therapy. It was concluded that erythropoietin corrects anemia in
patients undergoing hemodialysis, improves levels of protein and trace elements, and
improves the quality of life.

26. Schucker and Ward. (2005) discussed the pathophysiology of hyperphosphatemia

associated with end-stage renal disease and treatment with phosphate binders.
Phosphorus is an essential element necessary for the normal function of the human body,
required for skeletal construction and synthesis of DNA, proteins, and adenosine
triphosphate. In healthy individuals, serum phosphorus concentrations are maintained
between 2.5 and 4.5 mg/dL through diet and renal excretion. In renal insufficiency,
phosphorus excretion declines and hyperphosphatemia develops. The body's
compensation mechanisms cause secondary hyperparathyroidism and renal
osteodystrophy. Phosphate binders provide an effective means for managing serum
phosphate. Commercially available phosphate binders include calcium carbonate,
calcium acetate, sevelamer, lanthanum, and, rarely, aluminum hydroxide. Because of
aluminum's known toxicities, aluminum-based phosphate binders have a limited place in
therapy. Calcium carbonate's benefits are seen over a narrow gastric pH range, thereby
limiting the drug's utility. Calcium acetate is effective over a wide pH range. Other
phosphate binders, including sevelamer hydrochloride and lanthanum carbonate, have
recently entered the market, but their use remains controversial. They concluded if left
untreated, hyperphosphatemia can result in secondary hyperparathyroidism, renal
osteodystrophy, and metastatic calcification of blood vessels and soft tissue. The
treatment of hyperphosphatemia in patients with chronic renal failure includes dialysis,
dietary phosphorus restrictions, phosphate-binding medications, and vitamin D analogs.
Selection of phosphate binders should be based on patient characteristics, including
serum phosphate, serum calcium, and intact parathyroid hormone concentrations, and
patient tolerability.

27. Cupisti et al. (2004) evaluated the dietary habits of hemodialysis patients with
hyperphosphatemia and the effects of a dietetic intervention focused on limiting dietary
phosphate load. In a cross-sectional dietary evaluation and prospective intervention study
at hospital hemodialysis units of Pisa and Pistoia, Italy they selected forty-three stable
adult hemodialysis patients, 20 of whom had phosphorus serum levels >5.5 mg/dL.
Intervention was analysis of dietary composition and of the effects of individual dietetic
counseling in an attempt to reduce phosphorus intake while preserving the same protein
intake. They measured the differences in nutrient intake between normophosphatemic
and hyperphosphatemic patients, and changes in dietary phosphorus and phosphorus-
protein ratio, serum phosphate, and calcium-phosphate product after dietetic intervention.
They detected no major differences in nutrient intake between hyperphosphatemia and
normophosphatemia patients, apart from a lower phosphorus-protein ratio (13.1 +/- 1.7
versus 14.1 +/- 2.1 mg/g, P < .05) in the former. After dietetic intervention in the
hyperphosphatemia patients, phosphate and calcium intake decreased significantly (by
100 mg on average), whereas dietary protein did not change. A further decrease of the

12
dietary phosphate-protein ratio (12.5 +/- 1.8 mg/g, P < .05) also occurred. Serum
phosphate showed a trend to decrease in the intervention group, whereas the serum
calcium-phosphate product decreased significantly (from 66.8 +/- 13.1 to 61.0 +/- 13.8
mg2 /dL2, P < .05). They confirmed that in compliant and motivated patients, individual
dietetic counseling may be useful in reducing phosphate load and in limiting the
phosphate burden related to an adequate protein intake, with a potentially favorable
impact on calcium-phosphate retention. A phosphate-controlled diet has a role in an
integrated therapeutic approach to hyperphosphatemia and positive calcium-phosphorus
balance in hemodialysis patients

28. IKTZLER et al. (1994) studied amino acid and albumin losses during hemodialysis.
Protein and calorie malnutrition are prevalent in chronic hemodialysis (HD) patients and
has been linked to increased mortality and morbidity in this patient population. Concern
has been raised that the open pore structure of high flux membranes may induce the loss
of more amino acids (AA) compared to low flux membranes. To address this issue, they
prospectively analyzed pre- and post-HD plasma AA profiles with three different
membranes in nine patients. Simultaneously, they measured dialysate AA losses during
HD. The membranes studied were: cellulosic (cuprophane-CU), low flux
polymethylmethacrylate (LF-PMMA), and high flux polysulfone (HF-PS) during their
first use. Their results showed that pre-HD plasma AA profiles were abnormal compared
to controls and decreased significantly during HD with all dialyzers. The use of HF-PS
membranes resulted in significantly more AA losses into the dialysate when compared to
LF-PMMA membranes (mean so; 8.0 2.8 g/dialysis for HF-PS, 6.1 1.5 g/dialysis for LF-
PMMA, p <0.05, and 7.2 2.6 g/dialysis for CU membranes, P =NS). When adjusted for
surface area and blood flow, AA losses were not different between any of the dialyzers.
They also measured dialysate AA losses during the sixth reuse of the HF-PS membrane.
Losses of total AA increased by 50% during the sixth reuse of HF-PS membrane
compared to its first use. In addition, albumin was detected in the dialysate during the
sixth reuse of HF-PS membrane. We therefore measured albumin losses in all patients
dialyzed with HF-PS membranes as a function of reuse. Albumin losses increased
significantly beyond 15 reuses. Average albumin losses were 1.5 1.3 g/dialysis below the
15th reuse, but increased to 9.3 5.5 g/dialysis during the 20th reuse. They concluded that
the abnormal plasma AA profile in HD patients is further exacerbated with hemodialysis
for most of the individual amino acids, and that dialysate AA losses are modulated by
membrane characteristics and reuse. Further, HF-PS membranes with reuse numbers over
15 lose substantial amounts of albumin in the dialysate.

29. Vladimir Teplan and Olga Mengerova. (1997) studied an individualized

supplemented diet in hemodialysis patients to develop and test an individualized dietary
program for long-term hemodialysis patients with malnutrition. They started a metabolic
study with a 2-week dietary questionnaire to determine eating habits of patients and to
estimate intake of protein and energy. Forty-two patients with signs of malnutrition
receiving regular hemodialysis treatment were monitored for a period of 2 months. A
long-term dietary regimen was developed by a DIETA computer program with a database
containing the compositions of all used dishes of Czech cuisine. When a patient was
unable to receive the recommended dose of a nutrient, the diet was supplemented with

13
oral nutrition solutions. Patients were monitored for malnutrition and levels of S-albumin,
S-transferrin, body mass index, and Whitehead quotient. In results significant
improvement (P < .01) was seen in values of S-albumin, S-transferrin, body mass index,
and Whitehead quotient during the 2-moth follow-up period. Mild improvement in
protein catabolic rate (P < .05) was noted, and value of (urea) was >1 and not
significant. Compliance was in excess of 70%.They concluded that individualized diet
combined with adequate dialysis treatment significantly helps control the metabolic status
of patients with malnutrition who are on regular dialysis.

30. Sanai et al. (2010) reviewed that chronic renal failure (CRF) is recognized as a
significant medical problem in our part of the world. It refers to an irreversible
deterioration in renal function which classically develops over a period of years. The
disorder has five stages and the stage 5, also called end stage renal failure (ESRF), is a
severe illness and requires some form of renal replacement therapy (dialysis or renal
transplant). Cutaneous and mucosal changes are a common finding in patients of ESRF
and on long-term hemodialysis and can vary from each patient population to another. The
commonly seen dermatologic manifestations associated with ESRF are xerosis, pruritus,
pallor, fungal, bacterial and viral infections, xerostomia, scalp hair loss, nail changes like
half-and-half nails and splinter hemorrhages. The cutaneous manifestations related to
hemodialysis are skin infections, arteriovenous shunt dermatitis, gynecomastia, bullous
disease of dialysis etc. The present review does not highlight cutaneous changes of
diseases associated with the development of ESRF but it familiarizes clinicians about the
dermatologic changes in patients with chronic renal failure (CRF) undergoing
hemodialysis.

31. Ahmad et al. (2002) studied the frequency of complications during haemodialysis.The
commonly used renal replacement therapy for the end stage renal disease is the
maintenance haemodialysis. Only 30% are having approach to renal transplantation, a
gold standard treatment. The maintenance haemodialysis is the substitute for kidney
functions. On one hand it is blessing for chronic renal failure patients, the complications
may also occur on the other hand. This prospective study was conducted at Nephrology
section of Medical Unit-II, Nishtar Hospital, Multan. The objective of the study was to
determine the frequency of different complications during haemodialysis in patients
having end stage renal disease. The patients with acute renal failure having haemodialysis
were excluded from the study. The most frequently observed complications were
depressive illness, vomiting, fever, itching and hypotension. The causative relations of
the complications with other parameters were also assessed. Results indicate that
predialysis, thorough work up of patients and certain steps help to decrease the frequency
of complications.

32. Zarkoon et al. (2008) reported that hepatitis C infection is frequently noticed in
patients on hemodialysis. This study was conducted to estimate the frequency of hepatitis
C virus infection in patients on long term hemodialysis and to determine its risk factors. It
was a cross-sectional analytical study conducted at Sandeman Provincial Hospital, Quetta
from January 2006 to June 2007. Patients on long-term hemodialysis in Nephrology unit
were studied. Their medical records were reviewed for the presence of anti-HCV

14
antibodies and any risk factors. Ninety-seven patients on hemodialysis were included.
Out of these, 23 (23.7%) were found to be anti-HCV positive. The mean age of these
patients was 55.2±15.5 years while for anti-HCV negative patients 54.9±15.1. There were
18(78.3%) males in the HCV positive group while 46(62.2%) males in HCV negative
group. The mean duration of dialysis among HCV positive patients was 2.9±2.7 years
while 1.51±0.86 years for HCV negative ones. Anti-HCV positive group had
significantly greater proportion of patients with dialysis for more than 2 years (43.5% vs
9.5%). No significant difference was found in other risk factors. When years of dialysis
were treated as categorical variable, significant difference between anti-HCV positive
and negative groups was found. The risk of getting HCV infection was significantly
associated with increasing years of dialysis (p-value 0.002).They concluded that patients
on hemodialysis has 23.7% positivity for anti-HCV in our setup and history of dialysis
for more than two years is a significant risk factor for it.

33. Foley et al. (200) discussed the effect of hemoglobin levels in hemodialysis patients
with asymptomatic cardiomyopathy. Hemoglobin levels below 10 g/dL lead to left
ventricular (LV) hypertrophy, LV dilation, a lower quality of life, higher cardiac
morbidity, and a higher mortality rate in end-stage renal disease. The benefits and risks of
normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac
disease are unknown. One hundred forty-six hemodialysis patients with either concentric
LV hypertrophy or LV dilation were randomly assigned to receive doses of epoetin
designed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48
weeks. The primary outcomes were the change in LV mass index in those with concentric
LV hypertrophy and the change in cavity volume index in those with LV dilation. In
patients with concentric LV hypertrophy, the changes in LV mass index were similar in
the normal and low target hemoglobin groups. The changes in cavity volume index were
similar in both targets in the LV dilation group. Treatment-received analysis of the
concentric LV hypertrophy group showed no correlation between the change in mass
index and a correlation between the change in LV volume index and mean hemoglobin
level achieved (8 mL/m2 per 1 g/dL hemoglobin decrement, P = 0.009). Mean
hemoglobin levels and the changes in LV mass and cavity volume index were not
correlated in patients with LV dilation. Normalization of hemoglobin led to
improvements in fatigue (P = 0.009), depression (P = 0.02), and relationships (P = 0.004).
It was concluded that normalization of hemoglobin does not lead to regression of
established concentric LV hypertrophy or LV dilation. It may, however, prevent the
development of LV dilation, and it leads to improved quality of life.

15