Back to Basics Nephrology 2010 Major issues in Nephrology, Electrolytes, Acid-base disturbances

CKD

K/DOQI Classification of Chronic Kidney Disease StageGFR (≥3mo) Description (ml/min/1.73m 2 ) (ml/min/1.73m 2 ) 1  90 Damage with normal GFR 1  90 Damage with normal GFR Mild  GFR Mild  GFR Moderate  GFR Moderate  GFR Severely  GFR Severely  GFR 5 <15 Kidney Failure 5 <15 Kidney Failure

In this K/DOQI staging, “kidney damage” means: Persistent proteinuriaPersistent proteinuria Persistent glomerular hematuriaPersistent glomerular hematuria Structural abnormality:Structural abnormality: – such as PCKD, reflux nephropathy

CHRONIC KIDNEY DISEASE Diagnosis: Acute vs. chronic: –Small kidneys on U/S or unenhanced imaging mean CKD –Diabetic CKD may still have normal sized kidneys

CHRONIC KIDNEY DISEASE Common causes of CKD: Diabetic nephropathy Vascular disease GN PKD

CHRONIC KIDNEY DISEASE Causes of CKD: Best to divide as proteinuric or non-proteinuric CKD Proteinuric is much more likely to have deterioration in GFR and higher cardiovascular morbidity and mortality

CHRONIC KIDNEY DISEASE Treatment Delay progression: Treat underlying disease i.e. good glucose control for DM BP control to 130/80, (the current target) ACEI or ARB has extra benefit for proteinuric CKD Lower protein diet…maybe

CHRONIC KIDNEY DISEASE Treatment of the consequences of decreased GFR: –PO4: decrease dietary intake PO4 binders such as CaCO3 –Hypocalcemia: CaCO3, 1,25 OH D3

CHRONIC KIDNEY DISEASE Treatment of the consequences of decreased GFR: –Anemia: Erythropoetin current target Hb

CHRONIC KIDNEY DISEASE Uremic Complications: Major: –Pericarditis –Encephalopathy –Platelet dysfunction

ARF

Pre renal and ATN most common causes ( quoted at 70% of cases of ARF) DDx: –Pre Renal –Intra Renal –Post Renal

U Na U Osm Fe Na Pre-Renal ATN Urine: Pre-Renal vs. Renal Assessment of Function Fe Na = U/P Na U/P Cr X 100 > 500< 1% > 40 < 350> 2% < 20 Pigmented granular casts found in up to 70% of cases of ATN

Fe Urea Pre-Renal ATN Urine: Pre-Renal vs. Renal Assessment of Function Fe Urea = U/P Ur U/P Cr X 100 > 55 < 35 FeUrea might be useful to Dx pre renal ARF in those who received diuretics…but not all studies support its use.

ARF Investigations: –Pre Renal: Urine tests as noted and responds to volume –Intra-Renal: look for GN, interstitial nephritis as well as ATN –Post Renal: Imaging showing bilateral hydronephrosis is highly specific for obstruction causing ARF

If cannot control these by other means: Hyperkalemia Pulmonary edema Acidosis Uremia (GFR < 10-15% for CRF) Dialysis: Who Needs It?

Hemodialysis is also used for intoxications with: –ASA –Li –Alcohols: i.e. methanol, ethylene glycol –Sometimes theophylline Dialysis: Who Needs It?

Na +

Hyponatremia Pseudo: –If total osmolality is high: hyperglycemia/ mannitol –If total osmolality is normal, could be due to very high serum lipoprotein or protein

Hyponatremia Volume status: –Hypovolemic: high ADH despite low plasma osmolality –High total volume: CHF/ cirrhosis have decreased effective circulating volume and high ADH despite low plasma osmolality

Hyponatremia Volume status: –If volume status appears normal: If urine osmolality is low: normal response to too much water intake…”psychogenic polydipsia” If urine osmolality is high: inappropriate ADH

Hyponatremia Treatment: –Hypovolemic: Replace volume –Decreased effective volume: Improve cardiac output if possible Water restrict –SIADH: Water restrict

Hyponatremia Treatment: –Rate of correction of Na: Not more than 10 mmol in first 24 h and not more than 18 mmol over first 48 h of treatment Or Central Pontine Myelinosis may occur

Potassium

Hyperkalemia Real or Not: –Hemolysis of sample –Very high WBC, PLT –Prolonged tourniquet time

Hyperkalemia Shift of K from cells: –Insulin lack –High plasma osmolality –Acidosis –Beta blockers in massive doses

Hyperkalemia Increased total body K: –Decreased GFR plus: High diet K KCl supplements ACEI/ARB K sparing diuretics –Decreased Tubular K secretion

TTKG Requirements: –Urine osmolality > 300 –Urine Na+ > 25 –Reasonable GFR TTKG = [urine K +  (urine osmol/serum osmol)] serum K + <7, esp < 5 = hypoaldosteronism U/P K + /U/P Osm

Hyperkalemia Treatment –IV Ca –Temporarily shift K into cells: Insulin and glucose Beta 2 agonists (not as reliable as insulin) HCO3 if acidosis present –Remove K

GFR

ASSESSMENT OF GFR:

(140-age) x Kg x1.2 Creat (x.85 for women) ASSESSMENT OF GFR: Cockroft-Gault estimated Creatinine clearanceCockroft-Gault estimated Creatinine clearance UCr x V PCr Need a Steady State for these to be valid Creatinine clearance formula:

Labs now calculate this for anyone who has a serum creatinine checked Use serum creatinine, age, gender Labs now calculate this for anyone who has a serum creatinine checked Use serum creatinine, age, gender MDRD eGFR

GFR, in mL/min per 1.73 m2 = (170 x (PCr [mg/dL])exp[-0.999]) x (Age exp[-0.176]) x ((Surea [mg/dL])exp[-0.170]) x ((Albumin [g/dL])exp[+0.318]) where SUrea is the serum urea nitrogen concentration; and exp is the exponential. The value obtained must be multiplied by if the patient is female or by if the patient is black. GFR, in mL/min per 1.73 m2 = (170 x (PCr [mg/dL])exp[-0.999]) x (Age exp[-0.176]) x ((Surea [mg/dL])exp[-0.170]) x ((Albumin [g/dL])exp[+0.318]) where SUrea is the serum urea nitrogen concentration; and exp is the exponential. The value obtained must be multiplied by if the patient is female or by if the patient is black. Simplified: GFR, in mL/min per 1.73 m2 = x ((serum creatinine) exp[-1.154]) x (Age exp[-0.203]) x (0.742 if female) x (1.21 if African American) Simplified: GFR, in mL/min per 1.73 m2 = x ((serum creatinine) exp[-1.154]) x (Age exp[-0.203]) x (0.742 if female) x (1.21 if African American) MDRD eGFR Do NOT memorize this formula

Limitations of GFR estimates: Not reliable for: extremes of weight or different body composition such as post amputation, paraplegiaextremes of weight or different body composition such as post amputation, paraplegia acute changes in GFRacute changes in GFR use in pregnancyuse in pregnancy eGFR greater than 60ml/min/1.73m 2eGFR greater than 60ml/min/1.73m 2

Proteinuria

Albumin vs. other protein –Dipstick tests albumin

PROTEINURIA Quantitative: –24 hour collection –ACR: random albumin to creatinine ratio –PCR: random protein to creatinine ratio

PROTEINURIA Microalbuminuria: less than dipstick albumin Can use albumin to creatinine ratio on random urine sample… best done with morning urine sample

Random Urine 24h Urine Random Urine 24h Urine ACR(g/mol)Albumin(mg/24h)PCR(g/mol)Protein(mg/24h) NormalMF<2.0<2.8<30<20<200 Micro- albuminuria MF Macro- albuminuria >30>300

Nephrotic Syndrome Definition: –> 3 g proteinuria per day –Edema –Hypoalbuminemia –Hyperlipidemia and lipiduria are also usually present

Nephrotic Syndrome Causes: –Secondary: DM, lupus –Primary: Minimal change disease FSGS Membranous nephropathy

Nephrotic Syndrome Complications: –Edema –Hyperlipidemia –Thrombosis…with membranous GN and very low serum albumin

Nephrotic Syndrome Treatment: –Treat cause if possible –Treat edema, lipids –Try to decrease proteinuria

Hematuria

Significance: ≥ 3 RBC's per hpf DDx: Is it glomerular or not? Glomerular: –RBC casts –Dysmorphic RBCs in urine –Coinciding albuminuria may indicate glomerular disease

Hematuria Other investigation: –Imaging of kidneys –Serum creatinine –Age over rule out urologic bleeding, i.e. referral for cystoscopy

Hematuria For glomerular hematuria without proteinuria DDx includes: –IgA nephropathy –Thin GBM disease –Hereditary nephritis

Ca ++, PO 4, Mg ++

Ca ++ and PO 4 -- Decreased GFR and increased PO4 Decreased Ca  1 OH of 25-OHD3 Increased PTH Renal osteodystrophy

Magnesium Hypomagnesemia: –GI loss/lack of dietary Mg –Renal loss: Diuretics Toxins esp cisplatin

Hypophosphatemia Shift Decreased total body PO 4 –GI loss/decreased intake –Renal loss Fanconi Syndrome? –Very rare renal tubular loss of: PO 4, amino acids, glucose, HCO 3 -

Acid-Base Approach to: –Resp or metabolic –Compensated or not –If metabolic: anion gap or not –Anion gap = Na - (Cl + HCO3)

Acid-Base “MUDPILES”: –Methanol –Uremia –Diabetic/alcoholic ketosis –Paraldehyde –Isopropyl alcohol –Lactic acid –Ethylene glycol –Salicylate Increased anion Gap acidosis:

Acid-Base Metabolic acidosis with normal serum anion gap can be due to: 1) GI losses of HCO3 2) Renal tubular acidosis

Acid-Base Hopefully will not need this. Normal renal response to acidosis is to increase ammoniagenesis and more NH4 will be found in the urine The “urine anion gap” is a way to estimate urinary NH4 Urine anion gap = urine (Na + + K + – Cl - ) If positive there is decreased NH 4 + production