CKD/CRF

-DEFN: o *CKD is defined as EITHER: kidney damage decreased function (decreased GFR) for 3 or more months -kidney disease can be dx w/out knowledge of its cause -kidney damage is usually ascertained by MARKERS: o -rather than by kidney biopsy -MARKERS of kidney damage: o *PROTEINURIA -persistent proteinuria is the PRINCIPAL MARKER of kidney damage -an albumin/creatinine RATIO greater than 30 mg/g in SPOT urine samples is usually: *considered ABNORMAL o *other markers include: -urine sediment -abnormalities in BLOOD and URINE chemistry -abnormal findings on imaging studies o *persons w/: -normal GFR- BUT w/ MARKERS of kidney damage are: *at INCREASED RISK for adverse outcomes of CKD -CRF implies: *PERMANENT damage to the kidney -the normal architecture is gradually REPLACED by SCAR TISSUE -the HALLMARK of RENAL FAILURE is: *ELEVATION of the CREATININE and BUN concs in the extra-cellular fluid caused by: -a FALL in the GFR *other fns of the kidney are also impaired, such as: -SYNTHESIS of renal HORMONES *a wide range of sxs accompany the various degrees of renal failure -several TERMS are used to describe chronic renal injury:

*CRF: -is the general term used to describe IRREVERSIBLE loss of GFR over a prolonged period of time- usually YEARS *CHRONIC RENAL INSUFFICIENCY: -implies MILD CRF *AZOTEMIA: -refers to an ELEVATION in the BUN and CREATININE levels, and DOES NOT imply:*any sxs OR overt clinical manifestations of kidney disease -azotemia occurs w/ BOTH chronic and acute renal failure *UREMIA: -is the SYMPTOMATIC phase of renal failure during which: *sxs and signs of renal dysfn are DETECTED -for many individuals- uremic manifestations do NOT appear UNTIL: *the GFR is LESS than 10 ml/min (normal 120 ml/min) *END-STAGE RENAL DISEASE (ESRD): -refers to any form of CHRONIC (ieIRREVERSIBLE) renal failure at a stage that: *PERMANENT renal replacement therapy is indicated in the form of:-dialysis/transplant *NORMAL renal architecture is LOST and: -REPLACED w/ COLLAGEN -as this occurs: *the SIZE of the KIDNEYS generally DECREASES

* HYPER-FILTRATION HYPOTHESIS: ***a popular explanation for the PROGRESSIVE

NATURE of CRF is termed: -the HYPER-FILTRATION HYPOTHESIS: *this hypothesis states that- the INTACT nephrons are EVENTUALLY INJURED by: -the increased plasma flow AND hydrostatic pressure *healthy remnant nephrons sustain damage as a result of: -LONG-TERM exposure to: *INCREASED capillary PRESSURE and FLOW *hyper-filtration injury leads to a CHARACTERISTIC glomerular injury pattern known as:

-FOCAL GLOMERULAR SCLEROSIS *this hypothesis explains why renal failure CONTINUES to progress even when: -the initial renal insult is self-limited *acidosis *eg- some forms of glomerulonephritis *Na retention/water overload *HYPER-FILTRATION INJURY can be DIMINISHED by: *CHF/edema -REDUCING glomerular HYDROSTATIC PRESSURE *hyperkalemia -several methods of lowering glomerular pressure have been tried in an attempt to: *slow or halt the progression of CRF *hypertension, *anemia/hyperlipidemia *renal osteodystrophy -Co-morbs: *CV Disease /vasculardisease/malnutrx/neuroretinopathy/change drug handling/dehydraxn *ESRD COMPLICATIONS

(low protein diet (= hyperfiltraxn injury)= RBF and Pgc

*INCREASED SNGFR (ie- HYPER-filtration) occurs by: DILATATION of AFFERENT glomerular arterioles, resulting in:enhanced single-nephron PLASMA FLOW filtration may also be enhanced by: *INCREASED EFFERENT arteriolar TONE

DIET: protein ( Pgc)/ K (cuz hyperkalemia-arrythmias)/ Na (vol overloadedema and CHF)/ water if (hyponatremia)/P (hyperP- soft tissue deposits/osteodystrophy)

-Drugs: CRF CLINICAL SX -GFR<10 - SUMMARY: FINDINGS IN CRF: HTN (ACE inhibor-eff art dilaxn) EDEMA (diuretics=Na/h20 excrexn)
-in pts w/ NEPHROTIC SYNDROME (give diuretics) 1. Ca/Vit D-calcitrol (hypoCa, hyperPTH) /serum proteins/ EPO/Hb (anemia) P(soft tissue calcifixn)/K (hyperkalemia)/Renin (= Ang 2= BP/vol)/proteinuria *edema may also develop b/c of a: -LOW SERUM ALBUMIN conc *albumin is the SOURCE of ONCOTIC PRESSURE that determines: -the amt of FLUID HELD in the vascular compartment

2.

-PREVENT RENAL OSTEO (low P, give Ca/calcitrol)

Specific CRF Sx details -*SODIUM RETENTION (Na excrexn) results in: -EXPANSION of the extra-cellular space, which is manifest as: 1. EDEMA 2. HYPER-TENSION require: a sodium-RESTRICTED DIET *HYPERKALEMIA restrict K+ intake -(arrhythmias/Gut K+ secrexn) *CHANGE DRUG DOSAGE IN CRF PTS: -its necessary to: *REDUCE the DOSE -or- EXTEND the dosing INTERVAL of drugs that are: -EXCRETED by the KIDNEYS -drugs that are REMOVED by the KIDNEYS include: *aminoglycosides/vancomycin/PCN/allopurinol/digo -in CONTRAST- LIVER drugs dont req adjustment: *ACID-BASE: METABOLIC ACIDOSIS (RETAIN ammonia) bone buffers w/Ca rel-> bone Dx) (retain P -> anion gap acidosis) *erythromycin/phenytoin/anticoags/narcotics *CNS (uremic toxin accumulation leads to lower seizure threshold) -Asterixis: involuntary hand jerking -> seizures *BONE DISEASE: RENAL OSTEODYSTROPHY *RENAL OSTEODYSTROPHY summary: ___________________________________________ DECREASED vitamin D HYPO-calcemia AND DECREASED excretion of PO4HYPER-phosphatemia -subtle ECG changes -peripheral sensory neuropathy *CARDIOVASC -dyslipidemia/-stroke -the ability to ELIMINATE a SALT LOAD may become COMPROMISED is some pts w/ CRF, leading to: *EXPANSION of the extra-cellular VOLUME -EDEMA formation: CHF + pulm edema -w/ ADVANCED renal failure- pts may develop an: DECREASED vitamin D AND HYPER PTH *ACUTE PERICARDITIS (infl./hemmor): (uremic toxins in pericardial space) -Sx: chest pain/SOB/pericardial frixn rub/TAMPONADE (hypoTN)

___________________________________________

(osteitis fibrosa cystica/osteomalacia-antacid) HYPO-calcemia ___________________________________________ Secretion of PTH RENAL OSTEODYSTROPHY

*METABOLIC/ENDOCRINE: *glucose intolerance AND insulin resistance*hyperlipidemia/DECREASED levels of testosterone AND estrogen (fertility)

ACUTE RENAL FAILURE

GFR/ Cr+BUN (cuz urea reab=prerenal-low flow) (Cuz Cr secreted so Cr= UT obstruxn/hydronephrosis) SAME-ratio can be same if both Cr/BUN inc *THREE CAUSES OF ARF: 1. PRE-RENAL *ie- functional *generalized or local *DECREASE in RBF and/or Pgc *ARF DEFIXN --acute renal failure is a common clinical syndrome -its DEFINED as: *increase of 0.5 mg/dL from baseline occuring over days (< 1 month) of: -the BUN or CREATININE *OR- 50% DECLINE in calculated GFR *its easy to miss the early changes -the clinical manifestations of this d/o arise from the: *DECLINE in GFR *and the INABILITY of the KIDNEY to EXCRETE toxic wastes produced by the body -its recognized clinically by: *RISING levels of BUN and CREATININE *and usually a REDUCED URINE OUTPUT -most forms are REVERSIBLE processes -most physicians accept the definition of acute renal failure as a: *RISE in plasma CREATININE of 0.5 mg/day *and- a RISE in BUN of 10 mg/dl/day *over several days (crystals/BPH) *occurs DISTAL to the cd (Dx: oliguria -> anuria -> BUN/Cr is over 20:1 Suprapubic//flank pain Urinalysis: hematuria +uric acid crystals (urea/Cr ratio > 1) or normal (if BPH) 3. POST-RENAL *ie- obstructive *obstruction in the urinary tract -BUN/Cr = 20:1 *occurs BEFORE the GLOMERULUS (Esp if have: poor tissue perfusion= hypoTN/ dehydraxn/hemorrhage/edema due to CHF or nephrotic or cirrhosis) 2. INTRA-RENAL *ie- structural *intrinsic renal disease leading to: -DAMAGED NEPHRONS -KIDNEYS ENLARGED (-> GFR + Cr +BUN)

Urinalysis: hematuria +uric acid crystals (urea/Cr ratio > 1) or normal (if BPH)

*DIAGNOSIS OF PRERENAL AZOTEMIA:

*DIAGNOSIS: IMAGING: -in pts w/ VOLUME DEPLETION/DEHYDRATION: * DX of obstruction depends on radiography: * history of vomiting diarrhea, or diuretic use Ultrasonography *physical exam may reveal: -poor skin turgor -orthostatic hypo-tension -tachycardia -conversely- pts w/ RELATIVE DECLINES in EFFECTIVE ARTERIAL BV from : *CHF , nephrotic syndrome, or cirrhosis *may show: -peripheral edema OR ascites URINALYSIS UNREMARKABLE, except for -urinalysis becomes ABNORMAL -increased # of hyaline and granular casts + less Na -tubular fn DIMINISHES (Cuz kidney NOT intrinsically diseased) -signs of UREMIA develop -Response to poor perfusion in ARF: -Na reab (SNS/aldo) (=less Na in urine) - H20 reab (ADH) -BUN/Cr = 20:1 (cuz -Na reab -> coupled urea reab -> BUN) PRERENAL AZOTEMIA -Causes: ATN (85%)/ AIN (allergy/eosinos)/Acute GN (RPGN) -Intrarenal SX: -GFR (intrarenal vasoconstrixn -> RPF + O2 to outer medulla/PST/TAL -Segmental patches of NECROTIC lesions *DIAGNOSIS OF POSTRENAL AZOTEMIA: -OBSTRUCTIVE (DISTAL TO CD) revible (Causes: intrarenal crystals, renal pelvis or ureter caliculi, or BPH or neoplasia/ chemoTx leads to acute urea nephropathy ( lysed cells -> urea -> uric acid crystals -> ARF!) -Dx: oliguria -> anuria -> BUN/Cr is over 20:1 -> REDUCE renal EXCRETORY FN: Suprapubic//flank pain -URINALYSIS: Casts: -made up of CELLULAR DEBRIS from injured or necrotic renal tubule cells are freq found in the DISTAL NEPHRON, where they: *IMPEDE the FLOW of URINE *the necrotic cells SHED into the tubular LUMEN: *DIAGNOSIS OF INTRARENAL ARF (#1): --BUN/Creatinine BOTH RISE and: *ratio NORMALIZES -IVP (b/c of the decline in renal fn- the IVP vis ualization of the collecting system in obstruction may not occur until 6-24 hrs after dye administration -CT scanning -or- retrograde pyelography

*not only by- OBSTRUCTING urine flow BUT -BACK-LEAK OF GLOMERULAR FILTRAXN=leave gaps along the tubular epithelia thru which glomerular filtrate can RE-ENTER the circulation, a process called: BACK-LEAK OF GLOMERULAR FILTRATE

-CT Scans and angiograms deliver the most toxic dyes to pt 4. Endo-geneous Toxins myoglobin, hemoglobin, and myeloma light chains

TOXIC SX: kidneys ENLARGED (PCT) TYPES OF INTRARENAL ARF: -MICROSCOPIC: *focal (patchy lesions) *proximal tubule NECROSIS and APOPTOSIS *ATN -ISCHEMIC (#1) (HYPOTXN -> STRUCL DAMAGE) OR TOXIC -*CAUSES of ischemic insult include: -hemorrhage -hypo-tension (cardiac sepsis) -often occurs in the presence of: *NSAIDs, and ACE inhibitors -these are ALL the causes that give rise to: *PRE-RENAL AZOTEMIA (high ratio, but tubules look normal)*BUT- the nephron cannot tolerate this state long SO: -condition EVOLVES from pre-renal to: INTRARENAL *CAUSES OF TOXIC ATN: 1. Antibiotics Aminoglycoside/ amphotericin B/cyclosporine: (used to prevent graft -vs- host disease in transplants) 2. Heavy Metals -cis-platin- dose-dependent -salts of mercury, arsenic, bismuth, silver, chromium 3. Radio-contrast Agents -this form of nephrotoxic ATN can present w/ an FENa o fLESS than 1% ISCHEMIC SX -EOSINOPHILIC HYALINE CASTS as well as PIGMENTED GRANULAR CASTS are common, esp in the: *distal tubules and- collecting ducts -these CASTS consist of:*TAMM-HALL PROTEIN -a specific urinary glycoprotein normally secreted by the cells of ascending thick limb and distal tubules *in conjunction w/ Hb/Mg. -other findings in ischemic ATN are: *interstitial edema *and- accumulations of leukocytes w/in dilated vasa recta *DISTAL CASTS: -hyaline-and- PIGMENTED HALLMARK of ATN *sloughed tubular epithelial cells -they're RBCs (pigmented)

*LABORATORY TESTS: -the URINE SEDIMENT in the EARLY phase of ATN usually contains: *renal tubular epithelial cells/ granular and epithelial cell casts -b/c TUBULAR FN is IMPAIRED: *the kidney's ability to conserve Na and maximally concentratethe urine is diminished -in pts whose AZOTEMIA is SECONDARY to PRERENAL CAUSES: *the urinary indices usually show: -urinary osmolality GREATER than 500 mOsm/kg water -urinary Na conc LESS than 10 mEg/L -urine-plasma creatinine ration LESS than 20 -these ranges are diagnostic in ~80% of cases **FE NA *FENa is GREATER than 1% in pt's w/:-ATN *FENa is LESS than 1% in pts w/:-PRE-RENAL AZOTEMIA *pts w/ radiocontrast induced acute renal failure often have: -FENa values LESS than 1% though ATN is PRESENT