Vetteth Chronic Kidney Disease

Chronic Kidney Chronic Kidney DiseaseDisease

Sandeep VettethSandeep Vetteth

Chronic Kidney DiseaseChronic Kidney Disease► A 54 year old woman is evaluated for a Cr of 1.3; 18 A 54 year old woman is evaluated for a Cr of 1.3; 18

months ago it was 0.9. She has a 5 year history of months ago it was 0.9. She has a 5 year history of DM 2, dyslipidemia and HTN well controlled with DM 2, dyslipidemia and HTN well controlled with lisinopril, HCTZ, and atenelol. She is also on lisinopril, HCTZ, and atenelol. She is also on glipizide and simvastatin. Hemoglobin is normal. glipizide and simvastatin. Hemoglobin is normal. What is the most appropriate for this patient?What is the most appropriate for this patient? 24 hour collection for proteinuria24 hour collection for proteinuria Kidney USGKidney USG Measurement of Urine micro albuminMeasurement of Urine micro albumin SPEPSPEP Measurement of HbA1CMeasurement of HbA1C

► In the United States, there is a rising incidence and In the United States, there is a rising incidence and prevalence of Kidney Disease.prevalence of Kidney Disease.

► Nearly 350,000 of these are on dialysis.Nearly 350,000 of these are on dialysis.► Also, there is an increasing prevalence of earlier Also, there is an increasing prevalence of earlier

stages of chronic kidney disease which unfortunately stages of chronic kidney disease which unfortunately is “under-diagnosed” and “under-treated” in the is “under-diagnosed” and “under-treated” in the United States.United States.

► In 2000, the National Kidney Foundation (NKF) Kidney In 2000, the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) Disease Outcomes Quality Initiative (K/DOQI) Advisory Board approved development of clinical Advisory Board approved development of clinical practice guidelines to define chronic kidney disease practice guidelines to define chronic kidney disease and to classify stages in the progression of chronic and to classify stages in the progression of chronic kidney disease. kidney disease.

Chronic Kidney DiseaseChronic Kidney Disease

Stages of Chronic Kidney Stages of Chronic Kidney DiseaseDisease

Stage 1Stage 1 Kidney damage with Kidney damage with normal or normal or ↑ GFR↑ GFR

GFR GFR ≥ 90 ≥ 90 ml/min/1.73 m2ml/min/1.73 m2

Stage 2Stage 2 Kidney damage with Kidney damage with mild mild ↓ GFR↓ GFR

GFR 60-89GFR 60-89

Stage 3Stage 3 Moderate Moderate ↓ GFR↓ GFR GFR 30-59GFR 30-59

Stage 4Stage 4 Severe Severe ↓ GFR↓ GFR GFR 15-29GFR 15-29

Stage 5Stage 5 Kidney failureKidney failure GFR GFR <15 (or <15 (or dialysis)dialysis)

Causes of End Stage Renal Causes of End Stage Renal DiseaseDisease

0%10%20%30%40%50%60%70%80%90%

100%

%

OtherInterstit NCystic KDGNBPDiabetes

USRDS Annual Data Report

Chronic Kidney DiseaseChronic Kidney Disease►Many terms are used to describe states of Many terms are used to describe states of

reduced glomerular filtration (GFR) not reduced glomerular filtration (GFR) not requiring renal replacement therapy; requiring renal replacement therapy; Chronic Renal InsufficiencyChronic Renal Insufficiency Chronic Renal Failure Chronic Renal Failure Renal InsufficiencyRenal Insufficiency Pre dialysis renal diseasePre dialysis renal disease Pre uremia Pre uremia Renal dysfunctionRenal dysfunction

► They are imprecise & poorly defined.They are imprecise & poorly defined.

►Measurement of GFRMeasurement of GFR Gold standard is Inulin Iothalamate.Gold standard is Inulin Iothalamate. Creatinine Clearance calculated by timed (24h) Creatinine Clearance calculated by timed (24h)

urine collection along with serum collection for urine collection along with serum collection for Creatinine.Creatinine.

Overestimate GFR when CKD is severe due to an Overestimate GFR when CKD is severe due to an increase in tubular secretion of creatinine.increase in tubular secretion of creatinine.

This factor can be corrected by cimetidine.This factor can be corrected by cimetidine.► Estimation of GFREstimation of GFR

More than 10 formulae for estimation of GFR. More than 10 formulae for estimation of GFR. MDRD most widely accepted now.MDRD most widely accepted now.

Chronic Kidney DiseaseChronic Kidney Disease

CKD – Risk FactorsCKD – Risk Factors►Diabetes MellitusDiabetes Mellitus► HypertensionHypertension► Cardiovascular Cardiovascular

DiseaseDisease►ObesityObesity►Metabolic SyndromeMetabolic Syndrome► Age and RaceAge and Race► Acute Kidney InjuryAcute Kidney Injury►MalignancyMalignancy

► Family history of Family history of CKDCKD

► Kidney StonesKidney Stones► Infections like Hep C Infections like Hep C

and HIVand HIV► Autoimmune Autoimmune

diseasesdiseases►Nephrotoxics like Nephrotoxics like

NSAIDSNSAIDS

CKD - CausesCKD - Causes►DiabeticDiabetic►Non DiabeticNon Diabetic

GlomerularGlomerular►Nephritic: PIGN, IgA, MPGNNephritic: PIGN, IgA, MPGN►Nephrotic: FSGS, Membranous, AmyloidosisNephrotic: FSGS, Membranous, Amyloidosis

Tubulointerstitial: Analgesic, Reflux, Ch. ObsTubulointerstitial: Analgesic, Reflux, Ch. Obs Vascular: Vasculitis, HTN, RASVascular: Vasculitis, HTN, RAS Cystic: ADPKDCystic: ADPKD CKD in transplantationCKD in transplantation

CKD - CausesCKD - Causes

► Abnormal Sodium-Water metabolismAbnormal Sodium-Water metabolism Edema, HypertensionEdema, Hypertension

► Abnormal Acid-base abnormalitiesAbnormal Acid-base abnormalities Metabolic Acidosis due to uremia or RTAMetabolic Acidosis due to uremia or RTA

► Abnormal hematopoesisAbnormal hematopoesis Anemia of CKDAnemia of CKD

► Cardiovascular AbnormalitiesCardiovascular Abnormalities LVH, CAD, Diastolic DysfunctionLVH, CAD, Diastolic Dysfunction

► Abnormal Calcium-Phosphorus metabolismAbnormal Calcium-Phosphorus metabolism Hyperphosphatemia, pruritus, arthralgiaHyperphosphatemia, pruritus, arthralgia HyperparathyroidismHyperparathyroidism Renal OsteodystrophyRenal Osteodystrophy

CKD - ManifestationsCKD - Manifestations

CKD - ManagementCKD - Management


►Diagnostic work up to decide underlying Diagnostic work up to decide underlying etiologyetiology

► Treatment of Hypertension and DyslipidemiaTreatment of Hypertension and Dyslipidemia► Treatment of AnemiaTreatment of Anemia► Treatment of HyperphosphatemiaTreatment of Hyperphosphatemia► Avoidance of Dehydration & Nephrotoxic Avoidance of Dehydration & Nephrotoxic

agentsagents► Proper Dosing of DrugsProper Dosing of Drugs► Preparation for Renal Replacement TherapyPreparation for Renal Replacement Therapy

CKD - EvaluationCKD - Evaluation

► Serum electrolytesSerum electrolytes► Urine spot protein analysis (24 hour no Urine spot protein analysis (24 hour no

longer recommended).longer recommended).► ANA, C3, C4ANA, C3, C4► SPEP, UPEPSPEP, UPEP► Kidney UltrasoundKidney Ultrasound► Urine sediment analysisUrine sediment analysis► BiopsyBiopsy

Evidence of glomerular disease without diabetesEvidence of glomerular disease without diabetes Sudden onset of nephrotic syndrome or Sudden onset of nephrotic syndrome or

glomerular hematuriaglomerular hematuria

CKD - EvaluationCKD - Evaluation



► Treatment of Hypertension and DyslipidemiaTreatment of Hypertension and Dyslipidemia ► Treatment of AnemiaTreatment of Anemia► Treatment of HyperphosphatemiaTreatment of Hyperphosphatemia► Avoidance of Dehydration & Nephrotoxic Avoidance of Dehydration & Nephrotoxic


CKD - HypertensionCKD - Hypertension► Anti-Hypertensive AgentsAnti-Hypertensive Agents

Single most important measure could be Single most important measure could be adequate BP control adequate BP control

Target BP <130/80 with minimal proteinuria and Target BP <130/80 with minimal proteinuria and BP<125/75 with significant proteinuria (>1g).BP<125/75 with significant proteinuria (>1g).

ACEIs and ARBs have been demonstrated to slow ACEIs and ARBs have been demonstrated to slow both diabetic and non-diabetic renal disease in both diabetic and non-diabetic renal disease in both experimental and human studies.both experimental and human studies.

Decrease the sodium intake to 2.5 g /dayDecrease the sodium intake to 2.5 g /day Usually requires more than 2 medications.Usually requires more than 2 medications. Diuretics enhance the antihypertensive and Diuretics enhance the antihypertensive and

antiproteinuric effects of other agents.. antiproteinuric effects of other agents..

CKD - DyslipidemiaCKD - Dyslipidemia►Dyslipidemia and Cardiovascular Dyslipidemia and Cardiovascular

morbidity morbidity Several studies like the 4D study showed no Several studies like the 4D study showed no

benefit of statins in dialysis patients.benefit of statins in dialysis patients. However, post hoc analysis of this data does However, post hoc analysis of this data does

suggest that the management of suggest that the management of dyslipidemia in CKD 2 – 4 improves cardiac dyslipidemia in CKD 2 – 4 improves cardiac mortality and morbidity.mortality and morbidity.

Dyslipidemia is frequently seen in glomerular Dyslipidemia is frequently seen in glomerular disease with proteinuria (nephrotic disease with proteinuria (nephrotic syndrome) and its control reduces syndrome) and its control reduces atherosclerosis related morbidity and atherosclerosis related morbidity and mortality.mortality.

CKD - AnemiaCKD - Anemia► Decreased quality of Decreased quality of

life with anemia.life with anemia.► Diagnosis of Diagnosis of

exclusion.exclusion.► Mostly apparent in Mostly apparent in

the stage 4 and 5 of the stage 4 and 5 of CKD.CKD.

► Due to decrease in Due to decrease in EPO production in EPO production in the kidney.the kidney.

CKD - AnemiaCKD - Anemia► ErythropoietinErythropoietin

Epoetin alfa :Procrit ® , Epogen®Epoetin alfa :Procrit ® , Epogen® Darbepoietin Alpha: ARANESP ®Darbepoietin Alpha: ARANESP ®

►Target Hg levels between 11g and 12g Target Hg levels between 11g and 12g but not exceeding 13g.but not exceeding 13g.

►Greater than 13g showed increased Greater than 13g showed increased mortality as per the CHOIR study.mortality as per the CHOIR study.

►Sufficient Iron should be administered Sufficient Iron should be administered to correct iron stores.to correct iron stores.

CKD - HyperphosphatemiaCKD - Hyperphosphatemia► Control of HyperphosphatemiaControl of Hyperphosphatemia

Due to decreased excretion in urine.Due to decreased excretion in urine. Control of hyperphosphatemia by dietary measures Control of hyperphosphatemia by dietary measures

slow progression in experimental models of CKD.slow progression in experimental models of CKD. Hyperphosphatemia leads to pruritus, calcification Hyperphosphatemia leads to pruritus, calcification

in synovial membranes, blood vessels and even in synovial membranes, blood vessels and even cardiac valves.cardiac valves.

Therapy includes Phosphorus restriction to Therapy includes Phosphorus restriction to 800mg/day and use of phosphrous binders with 800mg/day and use of phosphrous binders with food.food.►Calcium Carbonate (TUMS), Ca-acetate (PHOSLO)Calcium Carbonate (TUMS), Ca-acetate (PHOSLO)►LanthanumLanthanum►RenagelRenagel

CKD –CKD – Bone and Mineral Bone and Mineral diseasedisease

►Hyperparathyroidism:Hyperparathyroidism: High phosphorus and low Vitamin D High phosphorus and low Vitamin D

causing low calcium.causing low calcium. Monitor Intact PTH levels and keep Monitor Intact PTH levels and keep

between 100 and 500.between 100 and 500. Maintain Phosphorus and Calcium within Maintain Phosphorus and Calcium within

normal ranges.normal ranges. Vitamin D analog paricalcitol.Vitamin D analog paricalcitol. Calcimimetic agents like cinacalcet.Calcimimetic agents like cinacalcet.

CKD - NephrotoxicsCKD - Nephrotoxics► Avoidance of Dehydration/Nephrotoxic Avoidance of Dehydration/Nephrotoxic

AgentsAgents Drugs such as Aminoglycosides, NSAIDsDrugs such as Aminoglycosides, NSAIDs Avoiding exposure to Radio contrast agents.Avoiding exposure to Radio contrast agents. In presence of dehydration, even in absence of In presence of dehydration, even in absence of

renovascular disease, ACEIs or ARBs can renovascular disease, ACEIs or ARBs can aggravate renal dysfunctionaggravate renal dysfunction

Dehydration is frequent in tubulo-interstitial Dehydration is frequent in tubulo-interstitial disorders where urinary concentration is disorders where urinary concentration is impaired. impaired.

Proper Dosing of Drugs eg. AllopurinolProper Dosing of Drugs eg. Allopurinol

CKD – Medication DosingCKD – Medication Dosing► Proper Dosing of DrugsProper Dosing of Drugs

Uremia affects GI absorption; eg Iron.Uremia affects GI absorption; eg Iron. Impaired plasma protein binding of drugs; eg Impaired plasma protein binding of drugs; eg

Dilantin.Dilantin. Increased volume of distribution; Increased volume of distribution; Excretion of many drugs depends upon the Excretion of many drugs depends upon the

kidney;kidney;►Some drugs used in normal dose will lead to nephrotoxic Some drugs used in normal dose will lead to nephrotoxic

effectseffects eg. Allopurinoleg. Allopurinol►Other drugs when used in normal dose will lead to other Other drugs when used in normal dose will lead to other

toxic effects eg. Vancomycin.toxic effects eg. Vancomycin.►Dose Reduction or Interval ExtensionDose Reduction or Interval Extension

CKD - RRTCKD - RRT►Preparation for Renal Replacement Preparation for Renal Replacement

TherapyTherapy Education for Options of Dialysis & Renal Education for Options of Dialysis & Renal

Transplantation for Renal ReplacementTransplantation for Renal Replacement Hemodialysis Vs Peritoneal DialysisHemodialysis Vs Peritoneal Dialysis Avoidance of Veni-puncture & insertion of Avoidance of Veni-puncture & insertion of

catheters in peripheral veins once GFR < catheters in peripheral veins once GFR < 60mls.60mls.

Timely placement of vascular access or Timely placement of vascular access or PD catheter.PD catheter.

CKD - RRTCKD - RRT► Indications (Absolute):Indications (Absolute):

Uncontrolled hyperkalemia and acidosisUncontrolled hyperkalemia and acidosis Uncontrollable hypervolemia (pulmonary edema)Uncontrollable hypervolemia (pulmonary edema) PericarditisPericarditis AMS and somnolence (advanced encephalopathy)AMS and somnolence (advanced encephalopathy) Bleeding diathesisBleeding diathesis

► Indications (Relative):Indications (Relative): Nausea, vomiting and poor nutritionNausea, vomiting and poor nutrition Metabolic acidosisMetabolic acidosis Lethargy and MalaiseLethargy and Malaise Worsening kidney function <10 ml or <15 ml in Worsening kidney function <10 ml or <15 ml in

diabeticsdiabetics

CKD - RRTCKD - RRT► Transplantation:Transplantation:

Preemptive Preemptive transplant carries transplant carries both patient and graft both patient and graft survival advantage.survival advantage.

Graft survival better Graft survival better with living donor with living donor kidneys.kidneys.

Immunosuppresion is Immunosuppresion is almost always a almost always a must.must.

CKD - RRTCKD - RRT►Transplantation:Transplantation:

Diseases like FSGS may reccur early in the Diseases like FSGS may reccur early in the transplanted kidney.transplanted kidney.

Increased risk for infection, bone loss, Increased risk for infection, bone loss, cardiovascular disease.cardiovascular disease.

Contraindications:Contraindications:►Malignancy (recent or metastatic)Malignancy (recent or metastatic)►Current infectionCurrent infection►Severe extra renal diseaseSevere extra renal disease►Active use of illicit drugsActive use of illicit drugs

CKD - SummaryCKD - Summary► In creasing prevalence of CKD in the In creasing prevalence of CKD in the

population.population.►Early detection and prevention of Early detection and prevention of

progression. progression. ►Early involvement of nephrologists in Early involvement of nephrologists in

the care (when GFR<30).the care (when GFR<30).►Treatment of Manifestations and Treatment of Manifestations and

complications.complications.►Renal Replacement TherapyRenal Replacement Therapy

Timely referral for AccessTimely referral for Access Timely Transplant Work up.Timely Transplant Work up.

Chronic Kidney DiseaseChronic Kidney Disease► A 70 yr old woman comes for F/U of recently A 70 yr old woman comes for F/U of recently

diagnosed CKD and HTN. She is asymptomatic. Her diagnosed CKD and HTN. She is asymptomatic. Her only medications is Lisinopril which has been titrated only medications is Lisinopril which has been titrated to its maximum dose in the last 3 months. She is to its maximum dose in the last 3 months. She is compliant and uses salt restriction. BP is 160/90. exam compliant and uses salt restriction. BP is 160/90. exam is normal except for trace pedal edema. Cr is 1.3, K is is normal except for trace pedal edema. Cr is 1.3, K is 5 and Urine Prot is 2.1 gm. Which of the following is 5 and Urine Prot is 2.1 gm. Which of the following is the most appropriate treatment for this patient?the most appropriate treatment for this patient? ChlorthalidoneChlorthalidone LosartanLosartan MetoprololMetoprolol MinoxidilMinoxidil AmlodipineAmlodipine

Vetteth Chronic Kidney Disease

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