AN UNUSUAL CASE OF AN UNUSUAL CASE OF RENAL FAILURERENAL FAILURE

Dr.P.ARUL. PGDr.P.ARUL. PG

Prof. VIJAYARAGAVAN’s UnitProf. VIJAYARAGAVAN’s Unit

60 years old female patient Sabira admitted with 60 years old female patient Sabira admitted with complaints of complaints of

FeverFever

Abdomen painAbdomen pain For 3 daysFor 3 days

Burning micturitionBurning micturition

H/o Presenting illnessH/o Presenting illness::Fever – High grade, intermittent , associated Fever – High grade, intermittent , associated with chills.with chills.

Abdomen pain – Lower abdomen and also in Abdomen pain – Lower abdomen and also in the flanks.the flanks.

Burning micturition+ Burning micturition+

No C/o vomiting.No C/o vomiting.

No C/o oliguria.No C/o oliguria.

No C/o Facial puffiness or leg swelling. No C/o Facial puffiness or leg swelling.

Past HistoryPast HistoryDM – 3 yearsDM – 3 years

HT – 6 monthsHT – 6 months

Personal HistoryPersonal History – Not a smoker or alcoholic or – Not a smoker or alcoholic or tobacco chewer.tobacco chewer.

Family HistoryFamily History – No H/o similar illness. – No H/o similar illness.

Contact HistoryContact History – No H/o contact with – No H/o contact with tuberculous patients.tuberculous patients.

Drug HistoryDrug History – No H/o ingestion of NSADS. – No H/o ingestion of NSADS.

General ExaminationGeneral ExaminationPt conscious Pt conscious

OrientedOrientedAfebrileAfebrileAnemicAnemic

Not jaundicedNot jaundicedNo cyanosisNo cyanosisNo clubbingNo clubbing

Pedal edema+Pedal edema+No generalised lymphadenopathyNo generalised lymphadenopathy

Vital ParametersVital ParametersBP 130 /80 BP 130 /80

Temp 98.4 FTemp 98.4 F

Pulse 80/minPulse 80/min

RR 18/minRR 18/min

Systemic examinationSystemic examinationCVS – SCVS – S11SS22 + No murmur. + No murmur.

RS – NVBS, No added sounds.RS – NVBS, No added sounds.

PA - Soft, No organomegaly, suprapubic PA - Soft, No organomegaly, suprapubic tenderness+.tenderness+.

CNS – No FND.CNS – No FND.

InvestigationsInvestigationsCBCCBC

WBC– 13.6 X 10WBC– 13.6 X 1033/ml. dc p61% l 38% e1%/ml. dc p61% l 38% e1%RBC – 3.98 X 10RBC – 3.98 X 1066 /ml /mlHB – 7.2 gm /dlHB – 7.2 gm /dl

MCH – 18.1 pgMCH – 18.1 pgMCHC – 29.6 gm/lMCHC – 29.6 gm/l

PLT – 2.9 lacsPLT – 2.9 lacsECG ECG - - WNLWNLCHEST XRAYCHEST XRAY – normal– normalURINE – Sugar nil, alb-nil, dep – 1 to 2 puscells URINE – Sugar nil, alb-nil, dep – 1 to 2 puscells

28/928/9 5/105/10 8/108/10 10/1010/10 25/1025/10

Blood Sugar – FBlood Sugar – F 131131 9090 9494 102102 8686 PPPP 207207 101101 150150 132132 117117

UreaUrea 150150 8888 7979 8080 101101Creatinine Creatinine 7.67.6 2.32.3 2.42.4 2.02.0 2.12.1SodiumSodium 138138 135135 135135 136136 138138PotassiumPotassium 4.14.1 4.04.0 3.83.8 4.14.1 4.24.2CalciumCalcium 7.87.8Phosphorus Phosphorus 4.64.6Uric AcidUric Acid 5.95.924 hrs U Protein 90 mg/l24 hrs U Protein 90 mg/lVolume 1500 ml Volume 1500 ml

U/S abdomenU/S abdomen – small left kidney, RT – hydro – small left kidney, RT – hydro uretero nephrosis.uretero nephrosis.

RK – 11 x 6.4 cms PCS dilated upper and middle RK – 11 x 6.4 cms PCS dilated upper and middle ureter measures 7 mm ureter measures 7 mm

LK – normal PCS 7.7 x 3.5 cmsLK – normal PCS 7.7 x 3.5 cms

CT abdomenCT abdomen – bilateral hydro nephrosis with small – bilateral hydro nephrosis with small left kidney.left kidney.

Urine C/sUrine C/s – 3/09/09 klebsiella grown, HS – 3/09/09 klebsiella grown, HS cefotaxime, amikacincefotaxime, amikacin

9/10/09 klebsiella grown, HS amikacin 9/10/09 klebsiella grown, HS amikacin

DIAGNOSISDIAGNOSIS – DM/SHT/UTI/CKD non – DM/SHT/UTI/CKD non oliguric/ anemia oliguric/ anemia

TREATMENT TREATMENT – –

Pt treated with cefotaxime, metronidazole, lasix Pt treated with cefotaxime, metronidazole, lasix and insulin.and insulin.

Pt taken over by nephrologist.Pt taken over by nephrologist.

HD done.HD done.

On 16/10/09 for RT – HUN DJ stent done by On 16/10/09 for RT – HUN DJ stent done by urologist. urologist.

DISCUSSIONDISCUSSION

DIABETES &KIDNEY RELATED DIABETES &KIDNEY RELATED COMPLICATIONSCOMPLICATIONS

DIABETIC NEPHROPATHYDIABETIC NEPHROPATHY GlomerulonephritisGlomerulonephritis Membranous nephropathyMembranous nephropathy Renal papillary necrosisRenal papillary necrosis Renovascular diseaseRenovascular disease Autonomic neuropathy of bladderAutonomic neuropathy of bladder UTI – Acute pyelonephritisUTI – Acute pyelonephritis Renal tuberculosisRenal tuberculosis Contrast nephropathyContrast nephropathy

Renal dysfunction in DMRenal dysfunction in DM Stage IStage I

Renal hypertrophy and hyperfilterationRenal hypertrophy and hyperfilteration UAER, GFR & RPF increasedUAER, GFR & RPF increased

Stage IIStage II GFR increasedGFR increased UAER & BP normalUAER & BP normal BM thickeningBM thickening Increased mesangial volumeIncreased mesangial volume

Stage IIIStage III Microalbuminuria or incipient nephropathyMicroalbuminuria or incipient nephropathy GFR normal or increasedGFR normal or increased UAER 30-300mg/24hrsUAER 30-300mg/24hrs BP increasedBP increased Increased BM thickening and fractional mesangial volume within the Increased BM thickening and fractional mesangial volume within the

glomeruliglomeruli Subsequently decrease in GFRSubsequently decrease in GFR

Stage IVStage IV Overt nephropathyOvert nephropathy HT, proteinuriaHT, proteinuria NS is commonNS is common GFR decreasedGFR decreased

Stage VStage V ESRDESRD Median survival of 7yrs from the development of persistent Median survival of 7yrs from the development of persistent

proteinuria if no intervention undertakenproteinuria if no intervention undertaken

Renal pathology in DMRenal pathology in DM

Size Size Larger & wt increase an average of 15%Larger & wt increase an average of 15% Increase in protein & RNA contentIncrease in protein & RNA content Increase in DNA synthesisIncrease in DNA synthesis Renal size increased till ESRD is establishedRenal size increased till ESRD is established Renal hypertrophy may be due to compensatory growth in Renal hypertrophy may be due to compensatory growth in

the face of glomerular lossthe face of glomerular loss PAS staining material get filled up in atropic ischemic PAS staining material get filled up in atropic ischemic

glomeruliglomeruli In DM renal volume continues to increase as UAER rises In DM renal volume continues to increase as UAER rises

to the level of overt proteinuriato the level of overt proteinuria

UAERUAER

24hrs(mg/day)24hrs(mg/day) overnightovernight

NormoalbuminuriaNormoalbuminuria <30<30 <20<20

MicroalbuminuriaMicroalbuminuria 30-30030-300 20-20020-200

Overt nephropathyOvert nephropathy >300>300 >200>200

ACR >2 predicts UAER >30/ACR >2 predicts UAER >30/µg/minµg/min Cut off for ACR in Cut off for ACR in

Male >2.5Male >2.5 Female >3.5Female >3.5

Renal papillary necrosisRenal papillary necrosis

Renal papillary necrosis (RPN) is characterized by Renal papillary necrosis (RPN) is characterized by coagulative necrosis of the renal medullary pyramids coagulative necrosis of the renal medullary pyramids and papillaeand papillae

Renal papillary necrosis generally affects individuals Renal papillary necrosis generally affects individuals who are in the middle decades of life or older who are in the middle decades of life or older

It is more common in women than in men It is more common in women than in men 60% of the patients have DM, 30% Urinary tract 60% of the patients have DM, 30% Urinary tract

obsruction, 15% have both.obsruction, 15% have both. Renal papillary necrosis is primarily a bilateral Renal papillary necrosis is primarily a bilateral

processprocess

Etiology Etiology PyelonephritisPyelonephritis Obstruction of the urinary tractObstruction of the urinary tract Sickle cell hemoglobinopathies, including sickle cell Sickle cell hemoglobinopathies, including sickle cell

traittrait TuberculosisTuberculosis Cirrhosis of the liver, chronic alcoholismCirrhosis of the liver, chronic alcoholism Analgesic abuseAnalgesic abuse Renal transplant rejection, Radiation, Renal vein Renal transplant rejection, Radiation, Renal vein

thrombosisthrombosis Diabetes mellitusDiabetes mellitus Systemic vasculitisSystemic vasculitis

Analgesic induced RPNAnalgesic induced RPN One of the most common and most preventable etiologic One of the most common and most preventable etiologic

factors is the use of analgesics. factors is the use of analgesics. In healthy individuals in whom renal arterial blood flow is not In healthy individuals in whom renal arterial blood flow is not

compromised, NSAIDs have little effect unless they are used compromised, NSAIDs have little effect unless they are used in excess. in excess.

The normal kidney is not relying on the vasodilatory effects of The normal kidney is not relying on the vasodilatory effects of prostaglandin to supply adequate perfusion. However, in prostaglandin to supply adequate perfusion. However, in patients who are predisposed to renal hypoperfusion, local patients who are predisposed to renal hypoperfusion, local prostaglandin synthesis protects the glomeruli and tubules prostaglandin synthesis protects the glomeruli and tubules from ischemia. The inhibition of prostaglandin synthesis by from ischemia. The inhibition of prostaglandin synthesis by NSAIDs that inhibit COX-1 and COX-2, removes this NSAIDs that inhibit COX-1 and COX-2, removes this protective mechanism and predisposes the kidney to further protective mechanism and predisposes the kidney to further renal hypoperfusion and, ultimately, ischemia. renal hypoperfusion and, ultimately, ischemia.

Additionally, a short course of NSAIDs has caused papillary Additionally, a short course of NSAIDs has caused papillary necrosis and nonoliguric renal failure in otherwise healthy necrosis and nonoliguric renal failure in otherwise healthy individuals as young as age 17 years. A case such as this may individuals as young as age 17 years. A case such as this may be an anomaly, but caution is warranted when prescribing be an anomaly, but caution is warranted when prescribing NSAIDs, and adequate hydration is recommended.NSAIDs, and adequate hydration is recommended.

Pathophysiology Pathophysiology Renal papillary necrosis is classified depending Renal papillary necrosis is classified depending

primarily on the patient's degree of impaired primarily on the patient's degree of impaired vasculature as vasculature as Focal (ie, involving only the tip of the papilla) or Focal (ie, involving only the tip of the papilla) or Diffuse (ie, involving the whole papilla and areas of the Diffuse (ie, involving the whole papilla and areas of the

medulla)medulla) Researchers recognize 2 pathologic forms of renal Researchers recognize 2 pathologic forms of renal

papillary necrosis—the papillary necrosis—the medullary formmedullary form and the and the papillary formpapillary form. .

Patients with medullary ischemia develop decreased Patients with medullary ischemia develop decreased glomerular filtration rates, salt wasting, an impaired glomerular filtration rates, salt wasting, an impaired ability to concentrate, and polyuria because the vasa ability to concentrate, and polyuria because the vasa rectae supply the medulla and serve the rectae supply the medulla and serve the countercurrent exchange mechanism. countercurrent exchange mechanism.

Normal kidney Hypoperfused kidney

Does not depend upon local Prostaglandins

for adequate perfusion

Depend upon local Prostaglandins

for adequate perfusion

NO EFFRECT

RENAL PAPILLARY NECROSIS

ANALGESICS – COX1/COX2 INHIBITORS

PresentationPresentation Renal papillary necrosis has a variable clinical course that Renal papillary necrosis has a variable clinical course that

ranges from a chronic, protracted, and relapsing form to an ranges from a chronic, protracted, and relapsing form to an acute, rapidly progressive form. acute, rapidly progressive form.

The acute progressive form is particularly rare, but the effects The acute progressive form is particularly rare, but the effects are devastating, resulting in death from septicemia and renal are devastating, resulting in death from septicemia and renal failure, requiring dialysis and potentially resulting in death.failure, requiring dialysis and potentially resulting in death.

Patients with the more common chronic form may remain Patients with the more common chronic form may remain asymptomatic until diagnosed incidentally.asymptomatic until diagnosed incidentally.

The most common presenting symptoms in symptomatic The most common presenting symptoms in symptomatic patients include fever and chills, flank and/or abdominal pain, patients include fever and chills, flank and/or abdominal pain, and hematuria. and hematuria.

Acute renal failure with oliguria or anuria is rare; when these Acute renal failure with oliguria or anuria is rare; when these symptoms develop, the disease may be fulminant, If renal symptoms develop, the disease may be fulminant, If renal function deteriorates suddenly in a patient with confirmed function deteriorates suddenly in a patient with confirmed diabetes or in a patient with a known history of chronic diabetes or in a patient with a known history of chronic obstruction and/or pyelonephritis, consider the diagnosis of obstruction and/or pyelonephritis, consider the diagnosis of papillary necrosis, even if the patient is asymptomatic.papillary necrosis, even if the patient is asymptomatic.

Diagnosis Diagnosis CT findings include CT findings include

(1) small kidneys, (1) small kidneys, (2) ring shadows in the medullae, (2) ring shadows in the medullae, (3) contrast-filled clefts in the renal parenchyma, (3) contrast-filled clefts in the renal parenchyma, (4) renal pelvic filling defects. (4) renal pelvic filling defects.

IVU findings include IVU findings include (1) shrinkage and irregularity of papillae, (1) shrinkage and irregularity of papillae, (2) desquamated papilla in situ, demarcated by contrast material as a (2) desquamated papilla in situ, demarcated by contrast material as a

ring shadow (commonly referred to as the ring sign); ring shadow (commonly referred to as the ring sign); (3) a calix without a papilla; (3) a calix without a papilla; (4) a partially calcified filling defect in the renal pelvis (4) a partially calcified filling defect in the renal pelvis (5) contrast-containing rice-grain–sized cavities in the papilla, which (5) contrast-containing rice-grain–sized cavities in the papilla, which

are pathognomonic for the medullary form of renal papillary necrosis. are pathognomonic for the medullary form of renal papillary necrosis. Ultrasonography findings may suggest the diagnosis late in the Ultrasonography findings may suggest the diagnosis late in the

course of the disease but is not sensitive enough to be course of the disease but is not sensitive enough to be confirmatory in the earlier. confirmatory in the earlier.

Excretory urography in a patient with renal papillary necrosis and pyeloureteritis cystica. There is bilateral loss of the renal mantle

with contrast tracking from the renal fornix in the lower pole of the right kidney. There is also multiple smooth filling defects in the ureter, caused by ureteritis cystica

Photograph of a gross section from the right kidney shows abscesses in the cortex (arrowheads)

and hemorrhagic infarcts in papillary regions (arrows), findings indicative of pyonephrosis and necrotizing papillitis, respectively.

Treatment Treatment Medical Medical

Acute disease may require broad-spectrum intravenous Acute disease may require broad-spectrum intravenous antibiotics, hydration, glycemic control, and urinary antibiotics, hydration, glycemic control, and urinary alkalinization. Cessation of analgesic.alkalinization. Cessation of analgesic.

Patients with sickle cell disease may require exchange Patients with sickle cell disease may require exchange transfusions transfusions

SurgicalSurgical Acute obstruction with concomitant urinary tract infection Acute obstruction with concomitant urinary tract infection

is a urologic emergency that requires immediate is a urologic emergency that requires immediate percutaneous nephrostomy to relieve the obstruction, percutaneous nephrostomy to relieve the obstruction, ureteral stent placement, or endoscopic retrieval of the ureteral stent placement, or endoscopic retrieval of the obstructing sloughed papillae obstructing sloughed papillae

Nephrectomy may be life-saving in patients with Nephrectomy may be life-saving in patients with overwhelming infection overwhelming infection

Other renal diseases in DMOther renal diseases in DM GlomerulonephritisGlomerulonephritis

Every form of glomerular disease reportedEvery form of glomerular disease reported Membranous nephropathy most commonlyMembranous nephropathy most commonly

Renal papillary necrosisRenal papillary necrosis More common in femaleMore common in female Can be asymptomaticCan be asymptomatic Microscopic hematuria is frequent & sterile pyuria is Microscopic hematuria is frequent & sterile pyuria is

typicaltypical Modest proteinuria is commonModest proteinuria is common

Renovascular diseaseRenovascular disease Increased incidenceIncreased incidence Increased frequwncy in association with PVDIncreased frequwncy in association with PVD HT is commonHT is common

UTIUTI Asymptomatic bacteruria in womenAsymptomatic bacteruria in women Increase in symptomatic UTI in pregnancyIncrease in symptomatic UTI in pregnancy

Acute pyelonephritisAcute pyelonephritis Leads to perinephric abcessLeads to perinephric abcess Urine culture may be negative with fever & flank Urine culture may be negative with fever & flank

tendernesstenderness Gram – ve organism commonGram – ve organism common 90% of cases of emphysematous pyelonephritis occur in pt. 90% of cases of emphysematous pyelonephritis occur in pt.

with DMwith DM Renal tuberculosisRenal tuberculosis

Increased risk of developing renal tuberculosisIncreased risk of developing renal tuberculosis Contrast nephropathyContrast nephropathy

Increased rise of renal deterioration of renal function Increased rise of renal deterioration of renal function following use of contrast mediafollowing use of contrast media

Autonomic neuropathy of bladderAutonomic neuropathy of bladder

Prevalence is 40% in long standing diabetesPrevalence is 40% in long standing diabetes

PathologyPathology SymptomsSymptoms Sign Sign

Destruction of Destruction of proprioceptive afferent proprioceptive afferent

fibresfibresAsymptomatic Asymptomatic

Decreased awareness of bladder Decreased awareness of bladder distension & then micturition at distension & then micturition at

progressively larger volumesprogressively larger volumes

Disruption of Disruption of parasympathetic parasympathetic

innervation to detrusor innervation to detrusor & efferent sympathetic & efferent sympathetic innervations to trigoneinnervations to trigone

NoctuiraNoctuira

Decrease in Decrease in daytime daytime

micturition micturition frequencyfrequency

Weakened bladder contraction & Weakened bladder contraction & incomplete emptying. Increased incomplete emptying. Increased

residual volumeresidual volume

Urethral sphincter Urethral sphincter dysynergydysynergy

Recurrent UTIRecurrent UTIFunctional incompetence of UV Functional incompetence of UV

junctionjunction

PrevalencePrevalence Type 1 DMType 1 DM Type 2 DMType 2 DM

MicroalbuminuriaMicroalbuminuria 1616 3838

Overt nephropathyOvert nephropathy 1515 1515

At diagnosisAt diagnosis 00 99

Investigation & treatment for Investigation & treatment for microalbuminuriamicroalbuminuria

Monitor serum creatinineMonitor serum creatinine Check retinopathyCheck retinopathy Investigate other causes of renal pathologyInvestigate other causes of renal pathology Screen for IHD & PVDScreen for IHD & PVD Screen & treat HT aggressivelyScreen & treat HT aggressively Assess lipid profileAssess lipid profile Discourage smokingDiscourage smoking Tighten glycemic controlTighten glycemic control

Albuminuria in type 1 DM and Albuminuria in type 1 DM and development of complicationsdevelopment of complications

UAERUAERPrevalence Prevalence of HT %of HT %

Prevalence of Prevalence of retinopathy %retinopathy %

Prevalence of Prevalence of blindness %blindness %

Prevalence of Prevalence of neuropathy %neuropathy %

NormoalbuminuriNormoalbuminuria a

2020 1212 11 2121

Microalbuminuria Microalbuminuria 4040 2828 66 3131

Macroalbuminuria Macroalbuminuria 8080 5858 1111 5050

Diabetic nephropathyDiabetic nephropathy Characterized by persistent albuminuria >300mg/24hrs or Characterized by persistent albuminuria >300mg/24hrs or

>200>200μμg/min on at least 2 occasions separated by 3-6 monthsg/min on at least 2 occasions separated by 3-6 months Since type 2 DM is 10-15 times more common than type 1 Since type 2 DM is 10-15 times more common than type 1

DM, the prevalence of type 2 diabetic nephropathy is DM, the prevalence of type 2 diabetic nephropathy is substantially highersubstantially higher

Gender:Gender: M:F in type 1 DM 1.7:1 M:F in type 1 DM 1.7:1 In type 2 DM 5:1In type 2 DM 5:1

Age at onset of DMAge at onset of DM:: Puberty – disproportionate increase in renal hypertrophy during the Puberty – disproportionate increase in renal hypertrophy during the

phase of puberty has been noted recentlyphase of puberty has been noted recently >50yrs – high prevalence of microalbuminuria than those diagnosed >50yrs – high prevalence of microalbuminuria than those diagnosed

before the age of 40yrsbefore the age of 40yrs

Indications for renal biopsyIndications for renal biopsy

Renal biopsy should be considered Renal biopsy should be considered In the absence of retinopathyIn the absence of retinopathy With sudden & rapid onset of proteinuria With sudden & rapid onset of proteinuria

(particularly if disease duration is less than 5yrs)(particularly if disease duration is less than 5yrs) Abnormal evolution without transition through Abnormal evolution without transition through

usual stages eg. The development of NS wothout usual stages eg. The development of NS wothout previous microalbuminuriaprevious microalbuminuria