Elevated Serum Creatinine, a simplified approach Primary Care Update Creighton University School of Medicine. April 27 th, 2018 Disclosure Slide I have no disclosures and have no conflicts with this presentation. 1
Review and understand serum creatinine value in the context of production and elimination of creatinine. Review the relationship between GFR and serum creatinine concentration. Review a simplified approach to elevated serum creatinine. Review the treatment options for various types of renal diseases leading to elevated serum creatinine. Case #1 A 25 year old muscular male is being seen for an elevated a serum creatinine of 1.4mg/dl. He is otherwise healthy, goes to the gym on daily basis and takes no OTC or prescription meds. He has a BP of 120/80 and a normal physical exam and serum chemistries. His urinalysis is also unremarkable. 2
Case # 1 continued The 24 hour urine collection showed creatinine clearance in the normal range (120 to 130ml/min). Elevated serum creatinine Serum creatinine concentration is a measure of production and elimination. Serum creatinine is a measure of diet, muscle mass and GFR. Serum creatinine of 1.5 may suggest a normal GFR in a body builder with large muscle mass and severely diminished GFR in a malnourished person. In acute settings like rhabdomyolysis, creatinine could be very high, even in absence of AKI. 3
Case #2 A 25 year old thin female is being seen for an elevated serum creatinine of 1.4mg/dl She has a prior history of urinary reflux as a child which was surgically corrected. Her baseline creatinine last noted 6 months ago was 1.2. She exercises every day and has no significant medical problems other than GERD. She recently started taking Tagamet on daily basis for symptom relief of reflux. She reports no NSAIDS intake. She has a BP of 120/80 and a normal physical exam and serum chemistries. Her urinalysis is unremarkable. Case #2 continued She was asked to stop Tagamet and a serum creatinine obtained a week after stopping Tagamet was back to her baseline, 1.2mg/dl. 4
Elevated serum creatinine Creatinine clearance is combination of filtration and secretion. Creatinine is freely filtered by the glomerulus. 10 to 20 percent of urine creatinine is secreted by proximal tubular cation exchange secretory transporters. This secreted portion of creatinine increases in CKD and decreases by certain agents which block the cation exchange transporter in the proximal tubule Cimetidine and Trimethoprim block creatinine secretion and can increase serum creatinine concentration without lowering GFR. Elevated serum creatinine Sickle cell disease and Nephrotic syndrome can enhance Proximal tubular creatinine secretion and can lower serum creatinine. GFR is lower than what is otherwise expected from serum creatinine concentration in these conditions. 5
Case #3 You are seeing a 25 year old clinic patient of yours who got admitted a day ago with one week history of severe nausea, vomiting and diarrhea. His BP was low and he was found to be very dehydrated on clinical exam. He has no significant PMH and serum creatinine is normal at baseline. Serum creatinine on admission was 4.0mg/dl. He was markedly oliguric. On admission he was started on intravenous NS at 150 ml per hour and the following day after 24 hours of receiving IV fluids the nurse told you that he is making 50 to 60 cc of urine per hour. His serum creatinine is still 2.5mg/dl. Case #3 continued Elevated serum creatinine GFR recovers once plasma volume is replete in cases of AKI from pure underlying effective arterial volume contraction, whereas serum creatinine may still be high. Serum creatinine restores to a normal value or patient s baseline in due course of time. IV fluids can be decreased or turned off once urine flow rate is restored in these cases. 6
Case #4 A 50 year old male office executive with an unremarkable PMH presents for a physical and was found to have a serum creatinine of 2.0mg/dl. There is no prior history of kidney disease, family history is negative for renal disease. His physical exam is unremarkable and his BP is 120/80. CMP shows a high serum creatinine of 2.0mg/dl and all the other electrolytes are normal and there is no acid base abnormality. Case # 4 Continued UA is unremarkable and dip stick is negative for albumin. Microscopy reveals benign urinary sediment with no cellular elements or casts. Spot urine protein to creatinine ratio is 0.15 7
Approach to renal disease First step is to identify Proteinuric vs. non Proteinuric Kidney Disease. Non proteinuric renal diseases typically have a urine protein to creatinine ratio less than 0.5 (normal 0.15 or less). Proteinuric Kidney disease typically has urine protein to creatinine ratio of more than 1, suggestive of 1 gram or more of protein excretion Approach to Renal Disease Non Proteinuric Kidney Disease Pre Renal Conditions leading to diminished effective arterial blood volume. Examples include CHF, Cirrhosis, Nephrosis and diuretic use Conditions leading to vascular compromise Example renal vascular disease 8
Approach to renal disease Intrinsic Renal Non Proteinuric Kidney Disease Tubular and interstitial Examples include ATN or AIN acute or chronic, Drug induced, heavy metal damage, autoimmune and infiltrative diseases. Examples include, NSAIDS, lead, cisplatin, lupus, sarcoidosis and Sjogren s syndrome Genetic Cystic diseases Examples include ADPKD, ARPKD and medullary cystic diseases. Approach to renal disease Non Proteinuric Kidney Disease Intrinsic Renal Burnt out glomerular disease can present with minimal proteinuria, patient usually has high serum creatinine Tubular proteinuria as seen in paraprotein related renal disease. Examples include, Multiple myeloma, cast nephropathy and light chain deposition disease Dip stick will be negative but urine protein to creatinine ratio on spot specimen will be positive. Truly should be classified as proteinuric (non albumin protein) kidney disease. 9
Approach to renal disease Non Proteinuric Kidney disease Post Renal Urinary obstruction from any reason, most common is prostate enlargement and pelvic tumors. Supra bladder obstruction has to be bilateral to cause a rise in serum creatinine, examples include tumors encasing ureters, bilateral stones and retroperitoneal fibrosis. Approach to Renal Disease Non Proteinuric Kidney disease Treatment includes treating the underlying cause Prerenal causes might need diuretic adjustment and treating underlying organ dysfunction. No specific treatment for chronic tubulointerstitial disease, minimize ongoing insult if known. Relief of obstruction in post renal. 10
Case # 5 A 50 year old male with an unremarkable PMH presents for a physical and was found to have a serum creatinine of 2.0mg/dl. There is no prior history of kidney disease, family history is negative for renal disease as well, physical exam is positive for1+ lower extremity edema and his BP is 160/90. CMP shows a high serum creatinine of 2.0mg/dl and all the other electrolytes are normal and there is no acid base abnormality. Urine dip stick is positive for 3+ protein, confirmed by spot urine protein to creatinine ratio of 3.0 Case #5 continued Urine microscopy revealed no cells or casts or a benign urinary sediment as most nephrologists would say. 11
Approach to Renal Disease Proteinuric Renal Disease Urinary sediment analysis provides clue to nephrotic vs. nephritic glomerular disorders Quantify protein excretion. Choice of 24 hour collection vs. spot urine protein to creatinine ratio. Exact quantity has therapeutic and prognostic implications in some glomerular diseases. Approach to Renal Disease Proteinuric Renal disease with benign urine sediment Nephrotic glomerulopathies like membranous and minimal change disease, primary or secondary Glomerulosclerosis, focal segmental, primary or secondary as in obesity and OSA. Hypertensive. Diabetic. Reflux nephropathy. Post inflammatory, example post lupus nephritis. Progressive nephron Loss as the underlying mechanism. Treatment. Ace inhibitors to control proteinuria, lower BP and treat underlying etiology. Immunosuppresives in some glomerulopathies 12
Light Microscopy Normal Glomerulus FSGS Light microscopy Normal glomerulus Membranous silver stain 13
Membranous Post anti PLA2R Era Normal glomerulus Immunoflorescenes Case # 6 A 35 year old female without any significant PMH presents with new onset fatigue, joint pains and a rash. Her physical exam is positive for a malar rash and 1+ lower. extremity edema and a BP of160/90. CMP shows a high serum creatinine of 2.0mg/dl and a bicarb of 20, all other electrolytes are normal. There is no prior history of kidney disease, family history is negative for renal disease as well. Urine dip stick positive for 2+protein, confirmed by spot urine protein to creatinine ratio of 2.0 14
Case # 6 continued UA micro shows 15 to 20 RBCs on HPF and few RBC casts. Case #6 continued Monomomorphic RBCs on phase contrast 15
Active sediment findings Electron micrograph Dysmorphic RBCs RBC cast Approach to Renal Disease Proteinuric renal disease with active urinary sediment Nephritic or Nephritic/Nephrotic Glomerular disease. Systemic diseases causing above picture include autoimmune diseases like lupus, infectious diseases like hepatitis B and hepatitis C as well as HIV. Idiopathic glomerular diseases causing nephritic picture, most common is membranoproliferative GN. 16
Approach to Renal Disease Check Complement Levels C3, C4 Complements low Hepatitis,Post Infectious, Lupus Complements Normal IgA Nephropathy,Rapidly Progressive Active Urinary Sediment Goodpatures syndrome AntiGBM disease ANCA Serologies,anti GBM antibodies canca Or panca diseases Wegners,Microscopic polyangitis Approach to Renal Disease Treatment of nephritic diseases Anti Hepatitis B and hepatitis C therapy Antireteroviral therapy for HIV. Steroids and Ace inhibitors for MPGN 17
Light Micrographs Normal Glomerulus Crescentic Glomerulonephritis Approach to renal disease Treatment of nephritic diseases with rapid progression, RPGN Steroids. Cyclophosphamide and various other immunosuppressive therapies. Plasma Exchange, especially in good pasture syndrome. Rituximab, (anti CD20 monoclonal antibody) 18
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