DIABETIC NEPHROPATHYROBERT QUIGLEY D.O.

SIERRA NEVADA NEPHROLOGY CONSULTANTS

OUTLINE

• DEFINE THE ILLNESS

• RECENT STATE OF AFFAIRS

• PATHOLOGY

• RISK FACTORS

• MEDICATION

• TREATMENTS

DIABETIC NEPHROPATHY IS A CLINICAL SYNDROME

• PERSISTENT ALBUMINURIA (>300 MG/D OR >200 ΜG/MIN) THAT IS CONFIRMED ON AT LEAST 2 OCCASIONS 3-6 MONTHS APART

• PROGRESSIVE DECLINE IN THE GLOMERULAR FILTRATION RATE (GFR)

• ELEVATED ARTERIAL BLOOD PRESSURE

• DIABETIC NEPHROPATHY IS THE LEADING CAUSE OF CHRONIC KIDNEY DISEASE IN THE UNITED STATES AND OTHER WESTERN SOCIETIES.

• ONE OF THE MOST SIGNIFICANT LONG-TERM COMPLICATIONS IN TERMS OF MORBIDITY AND MORTALITY FOR INDIVIDUAL PATIENTS WITH DIABETES.

• THE OVERALL PREVALENCE OF MICROALBUMINURIA AND MACROALBUMINURIA IN BOTH TYPES OF DIABETES IS APPROXIMATELY 30-35%.

• DIABETES IS RESPONSIBLE FOR 30-40% OF ALL END-STAGE RENAL DISEASE (ESRD) CASES IN THE UNITED STATES.

• THE EXTENDED LIFE SPAN OF DIABETIC PATIENTS DUE TO IMPROVED MANAGEMENT OF COMORBID CONDITIONS

• ACCEPTANCE OF PATIENTS FOR REPLACEMENT THERAPY WHO IN THE PAST WERE EXCLUDED.

Diabetic nephropathy is a clinical syndrome

DIABETIC NEPHROPATHY IS A CLINICAL SYNDROME

• DIABETIC NEPHROPATHY RARELY DEVELOPS BEFORE 10 YEARS’ DURATION OF TYPE 1 DM

• 3% OF NEWLY DIAGNOSED PATIENTS WITH TYPE 2 DM HAVE OVERT NEPHROPATHY.

• PEAK INCIDENCE IS USUALLY FOUND IN PERSONS WHO HAVE HAD DIABETES FOR 10-20 YEARS

• PATIENTS WHO HAVE NO PROTEINURIA AFTER 20-25 YEARS HAVE A RISK OF DEVELOPING OVERT RENAL DISEASE OF ONLY APPROXIMATELY 1% PER YEAR.

Incident counts & adjusted rates of ESRD, by primary diagnosis Figure 1.7 (Volume 2)

Incident ESRD patients. Adj: age/gender/race; ref: 2010 ESRD patients.

USRDS 2013 ADR

New end-stage renal disease patients with diabetes, reported at 44.5% in 2003.

Legend:

DIABETIC NEPHROPATHY IS A CLINICAL SYNDROME

• ESRD IS THE MAJOR CAUSE OF DEATH, ACCOUNTING FOR 59-66% OF DEATHS IN PATIENTS WITH TYPE 1 DM AND NEPHROPATHY.

• THE 5-YEAR SURVIVAL RATE WAS LESS THAN 10% IN THE ELDERLY POPULATION WITH TYPE 2

• 40% IN THE YOUNGER POPULATION WITH TYPE 1 DM.

ALBUMINURIA MARKER OR DESTROYER

• COMPARED TO NORMOALBUMINURIC PATIENTS, INDIVIDUALS WITH PERSISTENT MICROALBUMINURIA HAVE A THREE- TO FOUR-FOLD GREATER RISK TO PROGRESS TO OVERT PROTEINURIA AND LOSS OF CLEARANCE FUNCTION

• PATIENTS WITH TYPE 1 DIABETES MELLITUS, 20–45% PROGRESS TO OVERT PROTEINURIA OVER THE NEXT 10 YEARS, 30–60% REMAIN MICROALBUMINURIC, AND THE REST RETURN TO NORMOALBUMINURIA

• MICROALBUMINURIA INDEPENDENTLY PREDICTS CARDIOVASCULAR MORBIDITY

• MICROALBUMINURIA AND MACROALBUMINURIA INCREASE MORTALITY FROM ANY CAUSE IN DIABETES MELLITUS.

• MICROALBUMINURIA IS ALSO ASSOCIATED WITH INCREASED RISK OF CORONARY AND PERIPHERAL VASCULAR DISEASE AND DEATH FROM CARDIOVASCULAR DISEASE IN THE GENERAL NONDIABETIC POPULATION.

Charge and size of molecules prevent them from entering the urinary space

HYPERGLYCEMIA: BAD

• STIMULATES MESANGIAL CELL MATRIX PRODUCTION

• ADVANCED GLYCATION END PRODUCTS

• CYTOKINES, PROFIBROTIC ELEMENTS, INFLAMMATION, AND VASCULAR GROWTH FACTORS (VASCULAR ENDOTHELIAL GROWTH FACTOR, VEGF)

mesangial expansion

glomerular basement membrane thickening

glomerular sclerosis

RISK FACTORS FOR PROGRESSION

• GENES

• GLYCEMIC CONTROL

• RACE — BLACKS (3- TO 6-FOLD COMPARED TO CAUCASIANS), MEXICAN-AMERICANS, AND PIMA INDIANS

• OBESITY

• SMOKING

• HYPERTENSION

MEDICATIONS TO START

• METFORMIN-STILL THE GOAL STANDARD FOR STARTING MEDICATION-CONTINUE TO USE UNTIL GFR LESS TAN 30

• GLIPIZIDE CAN BE USED IN CONJUNCTION OR INSTEAD

• ACE/ARB

TREATMENT

• IMPROVED GLYCEMIC CONTROL

• ACE/ARB/SPIRONOLACTONE

• BARIATRIC SURGERY

• RISK FACTOR MODIFICATION-SMOKING

• EXERCISE

• DIET-LOW PROTEIN

• CHOLESTEROL TREATMENT-QRISK

WHEN TO SUSPECT SOMETHING ELSE

• THE ONSET OF PROTEINURIA LESS THAN FIVE YEARS FROM THE DOCUMENTED ONSET OF TYPE 1 DIABETES, IT IS HARDER TO DETERMINE FOR TYPE 2 SINCE ONSET/ TIME OF DIAGNOSIS VARIABLE

• THE ACUTE ONSET OF RENAL DISEASE. DIABETIC NEPHROPATHY IS A SLOWLY PROGRESSIVE DISORDER CHARACTERIZED BY INCREASES IN PROTEIN EXCRETION AND THE SERUM CREATININE CONCENTRATION OVER A PERIOD OF YEARS.

• THE PRESENCE OF AN ACTIVE URINE SEDIMENT CONTAINING RED CELLS IN A PREVIOUS NEGATIVE UA

• IN TYPE 1 DIABETES, THE ABSENCE OF DIABETIC RETINOPATHY OR NEUROPATHY, TYPE 2 MORE VARIABLE TRIAL OF BIOPSY ABOUT 50%●

• SIGNS AND/OR SYMPTOMS OF ANOTHER SYSTEMIC DISEASE • PROTEINURIA IN AN ELDERLY DM PATIENT WITH NO PREVIOUS HX OF THE SAME

Figure 1.15 Diabetic NHANES participants with glycosylated hemoglobin <7%, 1998-2012

Vol 1, CKD, Ch 1 19

Data Source: National Health and Nutrition Examination Survey (NHANES), 1988–1994, 1999-2004 & 2007–2012 participants aged 20 & older. Single-sample estimates of eGFR & ACR; eGFR calculated using the CKD-EPI equation. Abbreviations: ACR, urine albumin/creatinine ratio; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.