Tubulointerstitial Disease B wall

TIN Bruce R. Wall, MD, FACP March 4th, 2004 Cardiology fellowship -something goes wrong with…      Myocardium: acute +/- chronic ischemia, infiltrative processes, diastolic dysfunction, idiopathic cardiomyopathies – ―pump wears out‖ Coronary artery disease: imaging, stents, bypass, diagnosis and prevention – ―vessels wear out‖ Valvular disease: relative stenosis or leakage – ―valves wear out‖ Electrophysiology: EP studies, pacemakers Transplantation: less than 10,000 per year in US Nephrology fellowship— something goes wrong with… Renal artery: ASCVD, dissection, embolus  Renal vein: tumor, renal vein thrombosis  Ureter: retroperitoneal process, stone, obstruction  Glomerulus: primary or secondary disorders  Tubules: interstitial disease, auto-immune disorders, obstruction, infiltration  Hypertension, acid base disorders, endocrinopathies, transplantation, and dialysis  Our discussion today Approach to patient‘s with tubular disorders  Role of urinalysis in diagnosis of renal disease  Skip renal tubular acidosis type I, II, IV…  Drug-induced acute TIN  Case presentation  Urinalysis in the diagnosis of renal disease Gross hematuria with flank pain: helpful  Major diagnostic tool often provides information regarding renal disease & severity  Microscopic UA important information about resolution of active inflammatory process-acute GN UTI TIN  Early AM sample, centrifuged @3000 RPM color protein pH SG glucose  Color – clear, light yellow, white (pyuria), green (meth blue or propofol), red (several) red sediment = hematuria red supernatant = hemo or myoglobulin red supernatant with negative for heme? (Phenazopyridine vs beets…)  Protein – dispstick primarily detects albumin does not detect immunoglobulin or LCD semiquantitative only, @ concentration false-positive result after iodinated contrast  Urinalysis Urinalysis Sulfosalicylic acid test (SSA): detects all proteins, very helpful in setting of ―myeloma kidney”, where immunoglobulin LC form casts that obstruct tubules  Dipstick protein: insensitive for microalbuminuria, common screen in DM  24 hour urine protein determination: normal range up to 150mg per day nephrotic range suggests GN disease  Urinalysis    Hydrogen ion concentration – urine pH ranges from 4.5 to 8.0, depending on systemic acid-base balance. Urine pH helpful in metabolic acidosis Must consider urinary tract infection Osmolality – kidney excretes a wide range of solutes/mL, to keep the plasma OSM @ 285 mosmol/kg urinary concentration affected by ADH and patient‘s volume status or clinical status Dipstick detection of hematuria and pyuria should increase our use of microscopic examination of UA Urine sediment Crystals  Bacteria  Cells  Hematuria  Pyuria  Casts  Dysmorphic RBC‘s  Patterns…  acute interstitial nephritis   ―It‘s the economy, stupid…‖ probably applies to acute TIN: ‗it‘s the drugs, stupid‘ No one uses methicillin, since 17% patients treated for > 10 days developed TIN NSAIDs—particularly fenoprofen & indocin (No case reports for COX-2 inhibitors) PCN and cephalosporins Rifampin Sulfonamides, including loop diuretics Cimetidine and PPI‘s Ciprofloxacin > other quinolones 5-aminosalicylates (mesalamine) Clinical presentation of TIN         Probably needs several weeks with a first exposure Onset of TIN may be just a few days with a second exposure (with rifampin, as short as one day) Acute rise in creatinine, temporally related Fever, with or without rash Urine sediment with WBC‘s, casts, RBC‘s Eosinophilia and eosinophiluria > 75% of cases Less than 1000mg proteinuria per day Signs of tubulointerstitial damage (fanconi‘s or RTA) Diagnosis of TIN Suspected from H & P  Confirmed by renal biopsy  Gallium scanning may have some utility  Empiric trial of steroids, if non-bx candidate  Eosinophiluria present when eos > 1% of urinary WBC‘s by Hansel‘s stain sensitivity 67%, specificity 83% present in RPGN & atheroemboli often present, here at Presbyterian  Therapy of TIN Stop the offending drug… if patient improves, no further evaluation  No double blind controlled studies  Trial of corticosteroids – 1mg/kg and monitor creatinine for improvement  Example of TIN 80 yo mother of physician here at Presby  ARF, with creatinine of 7mg%  Non-nephrotic range proteinuria  Negative myeloma studies  No rash, yet low grade fever with eosinophiluria and hematuria  Small sized kidneys (9.5cm) too small for bx  Stopped her omeprazole, with prompt recovery  Case report    PS is a 78yo white male with history of HBP and chronic atrial fibrillation with normal GFR (creatinine of 0.9mg% on 12/15/03) CC: difficulty with breathing HPI: Patient noted increasing dyspnea, both with exertion, and at rest. He noticed increasing weakness, especially with walking more than 200 feet. He had fallen on 01/05/04. Xrays confirmed several rib fractures. Radiographs of upper thorax demonstrated compression fractures. Because of increased pain, he restarted CELEBREX, for 3 weeks. Case: continued Past history: BP chronic A Fib DJD  Medications: coumadin plendil vitamins celebrex  Family: non-contributory  Social: retired chemist; ex-smoker; daughter is PhD researcher at UT SW  ROS: No visual symptoms, or loss of vision. No dysuria, no urinary frequency. No swelling, no orthopnea, no sx‘s CHF.  Physical exam BP 160/100 P 90 T 98.6 R 16  GEN: WD WN preserved muscle mass  HEENT: negative; especially retina exam  Neck: no mass, no JVD, normal thyroid  Lungs: no rales, work of breathing was WNL  COR: IRR from Afib; soft SEM @ 2nd space  ABD: benign GU: no enlarged prostate  EXT: 2+ LE edema CNS: WNL  SKIN: no abnormalities  Lab profile WBC 6500 Hgb 12 Hct 31.9% ESR 90 plts 150K MCV normal  Na+ 131 K+ 7.8 Cl- 104 HCO3 17 BUN 107mg% Creatinine 9.8mg%  Urine: yellow 1.008 pH 7.5 glucose (-) trace protein trace blood 0-1 RBC/HPF SSA not done  Total protein 6.6g/dl; initial albumin 4.16g/dl small M spike on SPEP  Calcium 10.5mg/dl (with albumin 3.4mg%)  Additional lab: Renal sonogram: normal sized (13cm) without hydronephrosis or echogenicity  Foley revealed 200cc urine in bladder  ANCA level (+) 1:16 titer (low…)  Anti-GBM?  Rib fracture noted, post fall on January 5th  X-rays confirmed fx T6 and T7  MRI scan positive T6 to T8  CXR - ? Early overload vs pneumonia R base  Problems: 1) ARF (since creatinine was 0.9mg% @ 12/15/03) - differential diagnosis: Renal artery disease? Renal vein? Glomerular process? TIN? (medications?) Obstruction?  2) Hyperkalemia – therapy?  3) Hypercalcemia – cause?  Renal biopsy Indication: ARF, significant proteinuria, confused nephrologist  Complications? Bleeding (on lovenox & coumadin)  Results: myeloma kidney, severe tubulopathy  Therapy Dialysis  Plasmapheresis  Unfortunately, he returned to HD within 2 weeks… 