TUBULOINTERSTITIAL DISEASESANDRA DEL MUNDO, M.D. FPCP,DPSN

Tubulointerstial disease of the Kidney Characterized by histologic and functional abnormalities that involve the tubules and interstitium to a greater degree than the glomeruli and renal vasculature

Acute Interstitial NephritisDRUGSANTIBIOTICSANALGESICSDIURETICS

Presents with FEVER, EOSINOPHILIA (IMMUNE MECHANISM)INFECTION Bacteria ( streptococcal, staphylococcal, legionella, salmonella)

Viral( EBV, CMV, HIV)

Leptospiral

Chronic tubulointerstitial diseasesHereditary Polycystic kidney diseaseMedullary sponge kidneyMedullary cystic diseaseExogenous toxinsAnalgesic nephropathyLead nephropathyMisc( lithium, cyclosporine, heavy metals, slimming regimens)

Chronic tubulointerstitial diseasesMetabolic toxins HyperuricemiaHypercalcemia misc. ( hypokalemia, hyperoxaluria, cystinosis)Neoplastic disordersLeukemiaLymphomaMultiple myelomaMiscellaneous disordersChronic pyelonephritisChronic urinary tract obstructionRadiation nephritisVUR

Functional consequences of tubulointerstitial diseaseDefectReduced GRF

Fanconi syndrome

Hyperchloremic acidosisCausesObliteration of microvasculature and obstruction of tubulesDamage to PT reabsorption of glucose, amino acids, phosphate, and HCO3Reduced ammonia productionInability to acidify the collecting duct fluid Proximal HCO3 wasting

Functional consequences of tubulointerstitial diseaseDefectTubular or small molecular wt. proteinuria

Polyuria, isothenuria

Hyperkalemia

Salt wasting

CausesFailure of PT protein reabsorption

Damage to medullary tubules and vasculatureK+ secretory defects including aldosterone resistanceDistal tubular damage with impaired Na reabsorption

Analgesic nephropathyChronic analgesic intake 1 gm of phenacetin OD for 1-3 yearsPresents as:Chronic interstitial disease with obstructionChronic Renal FailurePapillary necrosisOverwhelming UTIUreteral ObstructionSterile pyuriaAcidosis / concentration defects

Papillary necrosisFOUND IN:1. DM2. OBSTRUCTION3. ANALGESIC ABUSE4. PYELONEPHRITIS5. TB OF THE KIDNEYSImpaired medullary perfusion deformity and sclerosis of papillaPapillary necrosis

Urinary tract infectionNormallyBladder urine is sterile ---becomes contaminated by: 1. Bacterial flora that colonize the urethral mucosa 2. Vagina 3. Surrounding skin

Significant Bacteriuria 100,000 organisms / mlMay still be significant even if < 100,0001. Acutely symptomatic women2. Symptomatic men3. Catheterized patientsUrinary tract infection

CLINICAL ENTITIES:1. CYSTITIS - bladder and urethra (lower tract)- dysuria, frequency, urgency, suprapubic tenderness2. PYELONEPHRITIS (upper tract)- flank pain, fever, Urinary tract infection

MAY OCCUR AS:1. Single event2. Recurrent infection2.1 RELAPSE -occurs 1-2 weeks after stopping antibiotics; common in kidney infection, structural abnormalities, chronic bacterial prostatitis 2.2 REINFECTION diff. organisms; new infectionUrinary tract infection

PATHOGENESIS: 3 Pathways:1. Blood stream2. Lymphatic channels3. Ascending infection through the uretersUrinary tract infection

PATHOGENESIS:- Gender and Sexual activity- Pregnancy - Obstruction- Neurogenic bladder dysfunction- Vesicoureteral reflux- Bacterial virulence factors- Genetic factors Urinary tract infection

PRINCIPLES OF TREATMENT:1.Diagnostic tests2. Predisposing factors3. Relief of symptoms does not always indicate bacteriologic cure4. Classify treatment Cure / Failure / RecurrentUrinary tract infection

PRINCIPLES OF TREATMENT:5. Choice of Drugs / duration of treatment6. Repeated infectionsUrinary tract infection

LEAD INTOXICATION* Children ingesting lead-based paints* Occupational exposure where lead containing metals or paints are heated to high temperature such as battery factories, smelters, salvage yards, firing ranges* Environmental lead exposuresLead nephropathy

Kidneys become atrophic as a result of ischemia to glomeruli, fibrosis of the tubulesHyperuricemic due to enhanced reabsorption of filtered uratesAcute gouty arthritis may occurHypertensionElevated serum level of leadLead nephropathy

Lead nephropathyDiagnosis: elevated serum levels of leadquantitation of lead excretion ffg infusion of Ca disodium edetateTreatment: remove source chelation

Acute Uric Acid nephropathyAcute over production of uric acid and extreme hyperuricemia seen in tumor lysis syndrome in px given cytotoxic drugs in lympho or myeloproliferative disorders

Prevention: allupurinol 200-800 mg/dIncrease urine vol with diureticalkalinization

Gouty NephropathyProlong form of hyperuricemiaPresence of crystalline deposits of uric acid and monosodium urate salts in kidney parenchyma.

Multiple myelomaOVERPRODUCTION OF ONE IMMUNOGLOBULINMONOCLONAL GAMMOPATHYBENCE JONES PROTEINSBONE INVOLVEMENTANEMIANEPHROTIC SYNDROME/ PYELONEPHRITIS/ RENAL FAILURE

MEDULLARY SPONGE KIDNEYDILATED COLLECTING DUCTS AND MEDULLARY CYSTSCALCULUS COLIC, HEMATURIA, INFECTION

POLYCYSTIC KIDNEY DISEASECYSTS ARE FORMED FROM MONOCLONAL PROLIFERATION OF THE TUBULAR EPITHELIUM REMAINING RENAL PARENCHYMA REVEALS VARYING DEGREES OF TUBULAR ATROPHY, INTERSTITIAL FIBROSIS, NEPHROSCLEROSIS

KIDNEYS ARE LARGE AND GRAPELIKE, CONTAINING CYSTS OF VARYING SIZES, REDUCING BY COMPRESSION THE FUNCTIONING TISSUE

AUTOSOMAL DOMINANT INHERITANCE

DISCOMFORT, PAIN, GROSS HEMATURIA, INFECTION, COLIC,RENAL FAILUREPALPABLE, BILATERAL, IRREGULAR, RENAL MASSES

POLYCYSTIC KIDNEY DISEASENEPHROLITHIASIS OCCURS IN 15-20% USUALLY CA OXALATE AND URIC ACID STONES

HYPERTENSION

HIGH HEMATOCRITS FOR THEIR LEVEL OF RENAL FUNCTION

FLUID OVERLOAD IS UNCOMMON BEC OF RENAL SALT WASTING

HEPATIC CYSTS, SPLEEN, PANCREAS, OVARY

INTRACRANIAL ANEURYSMSCOLONIC DIVERTICULAR DISEASE

DIAGNOSIS:

AT LEAST 3-5 CYST IN EACH KIDNEY

TREATMENT:

TREAT HYPERTENSION AND INFECTION AGGRESSIVELY ACE INHIBITORPOLYCYSTIC KIDNEY DISEASE

Proximal TubuleReabsorbs isosmotically about 55-60% of the filtrateAlmost all of the filtered glucose and amino acids are reabsorbed but only about 90% of the HCO3, 65% of the Na, and 55% of the Cl

PhosphateAmino acids

Comparison of Normal anion gap acidosis

Comparison of Normal anion gap acidosis

BARTTERS SYNDROME:- reabsorption of K- S/S - dilute urine, polyuria, hyperkaluria, - defective growthTx - K supplement, Spironolactone

CaCa BP

IDIOPATHIC FANCONI SYNDROME- reabsorption of glucose, amino acids, phosphates, bicarbonates, uric acid, water, sodium, potassium- S/S - growth failure, rickets, hypokalemia, polyuria- Tx Vitamin D

VITAMIN D RESISTANT RICKETS- REABSORPTION OF PHOSPHATE- S / S - PHOSPHATURIA - LOW SERUM PHOSPHATE - RICKETS- TX VITAMIN D

Thank you