Chronic Kidney Disease

Chronic Kidney Disease Sandeep Vetteth

Chronic Kidney Disease • 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 DM 2, dyslipidemia and HTN well controlled with lisinopril, HCTZ, and atenelol. She is also on glipizide and simvastatin. Hemoglobin is normal. What is the most appropriate for this patient? • 24 hour collection for proteinuria • Kidney USG • Measurement of Urine micro albumin • SPEP • Measurement of HbA1C

Chronic Kidney Disease • In the United States, there is a rising incidence and prevalence of Kidney Disease. • Nearly 350,000 of these are on dialysis. • Also, there is an increasing prevalence of earlier stages of chronic kidney disease which unfortunately is “under-diagnosed” and “under-treated” in the United States. • In 2000, the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) Advisory Board approved development of clinical practice guidelines to define chronic kidney disease and to classify stages in the progression of chronic kidney disease.

Stages of Chronic Kidney Disease

Causes of End Stage Renal Disease USRDS Annual Data Report

Chronic Kidney Disease • Many terms are used to describe states of reduced glomerular filtration (GFR) not requiring renal replacement therapy; • Chronic Renal Insufficiency • Chronic Renal Failure • Renal Insufficiency • Pre dialysis renal disease • Pre uremia • Renal dysfunction • They are imprecise & poorly defined.

Chronic Kidney Disease • Measurement of GFR • Gold standard is Inulin Iothalamate. • Creatinine Clearance calculated by timed (24h) urine collection along with serum collection for Creatinine. • Overestimate GFR when CKD is severe due to an increase in tubular secretion of creatinine. • This factor can be corrected by cimetidine. • Estimation of GFR • More than 10 formulae for estimation of GFR. • MDRD most widely accepted now.

Diabetes Mellitus Hypertension Cardiovascular Disease Obesity Metabolic Syndrome Age and Race Acute Kidney Injury Malignancy Family history of CKD Kidney Stones Infections like Hep C and HIV Autoimmune diseases Nephrotoxics like NSAIDS CKD – Risk Factors

CKD - Causes • Diabetic • Non Diabetic • Glomerular • Nephritic: PIGN, IgA, MPGN • Nephrotic: FSGS, Membranous, Amyloidosis • Tubulointerstitial: Analgesic, Reflux, Ch. Obs • Vascular: Vasculitis, HTN, RAS • Cystic: ADPKD • CKD in transplantation

CKD - Causes

CKD - Manifestations • Abnormal Sodium-Water metabolism • Edema, Hypertension • Abnormal Acid-base abnormalities • Metabolic Acidosis due to uremia or RTA • Abnormal hematopoesis • Anemia of CKD • Cardiovascular Abnormalities • LVH, CAD, Diastolic Dysfunction • Abnormal Calcium-Phosphorus metabolism • Hyperphosphatemia, pruritus, arthralgia • Hyperparathyroidism • Renal Osteodystrophy

CKD - Management

CKD - Management • Diagnostic work up to decide underlying etiology • Treatment of Hypertension and Dyslipidemia • Treatment of Anemia • Treatment of Hyperphosphatemia • Avoidance of Dehydration & Nephrotoxic agents • Proper Dosing of Drugs • Preparation for Renal Replacement Therapy

CKD - Evaluation

CKD - Evaluation • Serum electrolytes • Urine spot protein analysis (24 hour no longer recommended). • ANA, C3, C4 • SPEP, UPEP • Kidney Ultrasound • Urine sediment analysis • Biopsy • Evidence of glomerular disease without diabetes • Sudden onset of nephrotic syndrome or glomerular hematuria

CKD - Hypertension • Anti-Hypertensive Agents • Single most important measure could be adequate BP control • Target BP <130/80 with minimal proteinuria and BP<125/75 with significant proteinuria (>1g). • ACEIs and ARBs have been demonstrated to slow both diabetic and non-diabetic renal disease in both experimental and human studies. • Decrease the sodium intake to 2.5 g /day • Usually requires more than 2 medications. • Diuretics enhance the antihypertensive and antiproteinuric effects of other agents..

CKD - Dyslipidemia • Dyslipidemia and Cardiovascular morbidity • Several studies like the 4D study showed no benefit of statins in dialysis patients. • However, post hoc analysis of this data does suggest that the management of dyslipidemia in CKD 2 – 4 improves cardiac mortality and morbidity. • Dyslipidemia is frequently seen in glomerular disease with proteinuria (nephrotic syndrome) and its control reduces atherosclerosis related morbidity and mortality.

CKD - Anemia • Decreased quality of life with anemia. • Diagnosis of exclusion. • Mostly apparent in the stage 4 and 5 of CKD. • Due to decrease in EPO production in the kidney.

CKD - Anemia • Erythropoietin • Epoetin alfa :Procrit ® , Epogen® • Darbepoietin Alpha: ARANESP ® • Target Hg levels between 11g and 12g but not exceeding 13g. • Greater than 13g showed increased mortality as per the CHOIR study. • Sufficient Iron should be administered to correct iron stores.

CKD - Hyperphosphatemia • Control of Hyperphosphatemia • Due to decreased excretion in urine. • Control of hyperphosphatemia by dietary measures slow progression in experimental models of CKD. • Hyperphosphatemia leads to pruritus, calcification in synovial membranes, blood vessels and even cardiac valves. • Therapy includes Phosphorus restriction to 800mg/day and use of phosphrous binders with food. • Calcium Carbonate (TUMS), Ca-acetate (PHOSLO) • Lanthanum • Renagel

CKD – Bone and Mineral disease • Hyperparathyroidism: • High phosphorus and low Vitamin D causing low calcium. • Monitor Intact PTH levels and keep between 100 and 500. • Maintain Phosphorus and Calcium within normal ranges. • Vitamin D analog paricalcitol. • Calcimimetic agents like cinacalcet.

CKD - Nephrotoxics • Avoidance of Dehydration/Nephrotoxic Agents • Drugs such as Aminoglycosides, NSAIDs • Avoiding exposure to Radio contrast agents. • In presence of dehydration, even in absence of renovascular disease, ACEIs or ARBs can aggravate renal dysfunction • Dehydration is frequent in tubulo-interstitial disorders where urinary concentration is impaired. • Proper Dosing of Drugs eg. Allopurinol

CKD – Medication Dosing • Proper Dosing of Drugs • Uremia affects GI absorption; eg Iron. • Impaired plasma protein binding of drugs; eg Dilantin. • Increased volume of distribution; • Excretion of many drugs depends upon the kidney; • Some drugs used in normal dose will lead to nephrotoxic effectseg. Allopurinol • Other drugs when used in normal dose will lead to other toxic effects eg. Vancomycin. • Dose Reduction or Interval Extension

CKD - RRT • Preparation for Renal Replacement Therapy • Education for Options of Dialysis & Renal Transplantation for Renal Replacement • Hemodialysis Vs Peritoneal Dialysis • Avoidance of Veni-puncture & insertion of catheters in peripheral veins once GFR < 60mls. • Timely placement of vascular access or PD catheter.

CKD - RRT • Indications (Absolute): • Uncontrolled hyperkalemia and acidosis • Uncontrollable hypervolemia (pulmonary edema) • Pericarditis • AMS and somnolence (advanced encephalopathy) • Bleeding diathesis • Indications (Relative): • Nausea, vomiting and poor nutrition • Metabolic acidosis • Lethargy and Malaise • Worsening kidney function <10 ml or <15 ml in diabetics

CKD - RRT • Transplantation: • Preemptive transplant carries both patient and graft survival advantage. • Graft survival better with living donor kidneys. • Immunosuppresion is almost always a must.

CKD - RRT • Transplantation: • Diseases like FSGS may reccur early in the transplanted kidney. • Increased risk for infection, bone loss, cardiovascular disease. • Contraindications: • Malignancy (recent or metastatic) • Current infection • Severe extra renal disease • Active use of illicit drugs

CKD - Summary • In creasing prevalence of CKD in the population. • Early detection and prevention of progression. • Early involvement of nephrologists in the care (when GFR<30). • Treatment of Manifestations and complications. • Renal Replacement Therapy • Timely referral for Access • Timely Transplant Work up.

Chronic Kidney Disease • A 70 yr old woman comes for F/U of recently diagnosed CKD and HTN. She is asymptomatic. Her only medications is Lisinopril which has been titrated to its maximum dose in the last 3 months. She is compliant and uses salt restriction. BP is 160/90. exam 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 the most appropriate treatment for this patient? • Chlorthalidone • Losartan • Metoprolol • Minoxidil • Amlodipine

Chronic Kidney Disease