In the name of GOD

CHRONIC KIDNEY DISEASE

A. Jenabi MD

Ass. Professor of Medicine

and Nephrology,

iran University of medical Sciences Tehran , Iran

CHRONIC KIDNEY DISEASE

Chronic kidney disease (CKD) encompasses a spectrum of different pathophysiologic processes associated with abnormal kidney function, and a progressive decline in glomerular filtration rate (GFR).

chronic renal failure

IRREVERSIBLE LOSS OF GFR DENOTES PROGRESSION EVEN WHEN THE UNDERLYING CAUSE HAS BEEN ELIMINATED

Why call it chronic kidney disease?

why call it CKD as opposed to pre-ESRD, pre-dialysis or chronic renal failure ?

Pre-ESRD gives the impression that dialysis is the inevitable outcome of all kidney diseases and that there are no effective therapies to retard its progression. It is the equivalent of referring to life as pre-death.

The term renal failure also has a negative connotation and includes the term renal, which is not easily understood by patients and their families.

MOST OF THE CKD PATIENTS ARE ASYMPTOMATIC AND ARE DETECTED DURING SCREENING EITHER ROUTINE OR FOR UNRELATED ILLNESS

INCIDENCE OF CKD

At least 6% of the adult population in the USA has CKD at stages 1 and 2. An unknown subset of this group will progress to more advanced stages of CKD. An additional 4.5% of the U.S. population is estimated to have stages 3 and 4 CKD.

ESRD CKD

Uremia is a state of systemic poisoning

Due to cumulative effects of failure of many functions of kidney ESRD?

Pathophysiology of Chronic Kidney Disease

Two broad sets of mechanisms of damage : (1) initiating mechanisms specific to the

underlying etiology

(immune complexes and mediators of inflammation in certain types of glomerulonephritis, or toxin exposure (2) a set of progressive mechanisms, involving

hyperfiltration

and hypertrophy of the remaining viable nephrons

Pathophysiology of Chronic Kidney Disease

2

why a reduction in renal mass from an isolated insult may lead to a progressive decline in renal function over many years?

Pathophysiology of Chronic Kidney Disease

3

Increased intrarenal activity of the renin angiotensin axis appears to contribute both to the initial adaptive hyperfiltration and to the subsequent maladaptive hypertrophy and sclerosis, the latter, in part, owing to the stimulation of transforming growth factor (TGF-).

CKD Causes

CAUSE GLOMERULONEPHRITIS DIABETES HYPER TENSION POLYCYSTIC KIDNEY INTERSTITIAL NEPHRITIS OBSRUCTIVE NEPHROPATHY RENAL HYPOPLASIA HEREDITARY DISORDERS ADULTS 3+ 4+ 2+ 2+ 2+ 1+ RARE RARE CHILDREN 4+ RARE RARE 1+ 2+ 3+ 2+ 1+

CKD –Some Definitions

CKD results when a disease process damages the structural or functional integrity of the kidney.

This is clinically detected using either physical exam (hypertension), laboratory (hematuria, proteinuria, microalbuminuria) or imaging studies (CT, MRI, IVP or renal ultrasound).

Almost all patients with a GFR



60 ml/min/1.73m

2 have CKD.

However, since GFR declines normally with age (approximately 1ml/min/1.73 m 2 /year after age 20 ), a GFR between 60 - 90 ml/min/1.73m

2 in the elderly may not be indicative of the presence of CKD.

In order for patients to be classified as having CKD there must be some objective evidence on either physical exam, laboratory or imaging studies of kidney damage

.

Estimate the Glomerular Filtration Rate

Estimates of the glomerular filtration rate (GFR) based on the serum creatinine have a high degree of correlation with determinations of GFR based on inulin (gold standard) or iothalamate clearances. The later are more accurate but are cumbersome and costly.

These estimations also perform well when compared to collections of 24 hour urine which are difficult for patients to carry out and are often performed incorrectly.

Cockcroft-Gault equation [140-age(yr)]



weight(kg)]/[72



women).

serum Cr(mg/dl)] (



0.85 for MDRD equation 0.176



7-170



[serum creatinine (mg/dl)] - 0.999



[age] [0.762 if pt is female ] **[1.180 if pt is black ] **[BUN (mg/dl)] 0.170



[albumin (g/dl)] + 0.318.

Why can ’t one just use the serum creatinine ?

The serum creatinine alone is not an accurate measure of glomerular filtration rate. Creatinine , unlike inulin, is secreted by renal tubules ; and as renal function worsens the amount secreted increases. Normal ranges for serum creatinine are misleading because they do not take into account the age , sex , or weight of the patient.

Clinical examples

Consider the following two patients with identical serum Cr of 1.2 mg/ dL.

 Patient 1 - a 60 year old 50 kg woman  Patient 2 - a 30 year old 90 kg man

The first patient has a GFR of 39 ml/min/1.73 m

2

, which is markedly abnormal, while the second has a GFR of 115 ml/min/1.73 m

2

, well within the normal range.

CLASSIFICATION OF CKD-NKF

II III IV V

STAGE

I 0

DESCRIPTION WITH RISK FACTORS KIDNEY DAMAGE (WITH NORMAL OR  GFR) MILD MODERATE SEVERE KIDNEY FAILURE GFR(ml/min) >90 >90 60-89 30-59 15-29 <15

Conceptual Model for CKD

Normal Screening for CKD risk factors: diabetes hypertension age >60 family history US ethnic minorities Increased risk CKD risk reduction; Screening for CKD Complications 11.3 m 5.6% Damage



3.8% GFR Diagnosis & treatment; Treat comorbid conditions; Slow progression Estimate progression; Treat complications; Prepare for replacement 0.3 m 0.2% Kidney failure Replacement by dialysis & transplant CKD death

Measurement of albuminuria Albuminuria is also helpful for monitoring nephron injury apy in many forms of CKD While an accurate 24-h urine collection is the "gold standard" for measurement of albuminuria, the measurement of albumin-to-creatinine ratio in a spot first-morning urine sample is often more practical to obtain and correlates well. Persistence in the urine of > 17 mg of albumin per gram of creatinine in males and 25 mg albumin per gram of creatinine in females usually signifies chronic renal damage.

Microalbuminuria

refers to the excretion of amounts of albumin too small to detect by urinary dipstick or conventional measures of urine protein. It is a good screening test for early detection of renal disease, in particular, and may be a marker for the presence of microvascular disease in general.

Pathophysiology and Biochemistry of Uremia The uremic syndrome can be divided into manifestations in three spheres of dysfunction: (1) those consequent to the accumulation of toxins normally undergoing renal excretion, including products of protein metabolism. (2) those consequent to the loss of other renal functions , such as fluid and electrolyte homeostasis and hormone regulation.

(3) progressive systemic inflammation and its vascular and nutritional consequences

Hundreds of toxins that accumulate in renal failure have been implicated in the uremic syndrome;

nitrogenous excretory products include guanido compounds, urates and hippurates, products of nucleic acid metabolism, polyamines, myoinositol, phenols, benzoates, and indoles

SYSTEM GENERAL SKIN GIT CVS MUSCULO SKELETAL NS SYMPTOMS FATIGUE, WELL BEING ITCHING / BRUISING DRYNESS ANOREXIA / NAUSEA VOMITING / HICCUPS EDEMA, CHEST PAIN DYSPNEA BONE PAIN GROWTH FAILURE NUMBNESS / CRAMPS INSOMNIA / IMPOTENCE SIGNS WASTED,SALLOW COMPLEXION PALLOR, PIGMENTATION FROST, EXCORIATIONS GI BLEED HT / CARDIOMEGALY RUB / CRACKLES DEFORMITIES / MYOPATHY NEUROPATHY / ASTERIXIS MYOCLONUS / ACIDOSIS

Fluid and electrolyte disturbances

• Volume expansion (I) • Hyponatremia (I) • Hyperkalemia (I) • Hyperphosphatemia (I)

Endocrine-metabolic disturbances

• • • • • • • • • • • • • Secondary hyperparathyroidism (I or P) Adynamic bone (D) Vitamin D–deficient osteomalacia (I) Carbohydrate resistance (I) Hyperuricemia (I or P) Hypertriglyceridemia (I or P) Increased Lp(a) level (P) Decreased high-density lipoprotein level (P) Protein-energy malnutrition (I or P) Impaired growth and development (P) Infertility and sexual dysfunction (P) Amenorrhea (I/P) β 2 -Microglobulin associated amyloidosis (P or D)

Bone Manifestations of CKD

Flowchart for the development of bone, phosphate, and calcium abnormalities

Calcium, Phosphorus, and the Cardiovascular System • • Recent epidemiologic evidence has shown a strong association between hyperphosphatemia and increased cardiovascular mortality in patients with stage 5 CKD and even in patients with earlier stages of CKD Hyperphosphatemia and hypercalcemia are associated with increased vascular calcification

Fibroblast growth factor 23 (FGF-23

) is part of a family of phosphatonins that promotes renal phosphate excretion. Recent studies have shown that levels of this hormone, secreted by osteocytes, increases early in the course of CKD. It may defend normal serum phosphorus in at least three ways: (1) increased renal phosphate excretion; (2) stimulation of PTH, which also increases renal phosphate excretion; and (3) suppression of the formation of 1,25(OH)2D3, leading to diminished phosphorus absorption from the gastrointestinal tract. Interestingly, high levels of FGF-23 are also an independent risk factor for left ventricular hypertrophy and mortality in dialysis patients. Moreover, elevated levels of FGF-23 may indicate the need for therapeutic intervention (e.g., phosphate restriction), even when serum phosphate levels are within the normal range.

Calciphylaxis

Calciphylaxis is a devastating condition seen almost exclusively in patients with advanced CKD there is evidence of vascular occlusion in association with extensive vascular • • • calcification: advanced hyperparathyroidism increased use of oral calcium as a phosphate binder Warfarin is commonly used in hemodialysis pts, (decrease the vitamin K– dependent regeneration of matrix GLA protein)

Salt and pepper appearance skull And brawn tumor

Sub periosteal bone resorbsion and arterial calcification

Clavicles bone resorbsion

Rugger jersey appearance of skeletal vertebrae

Multiple brawn tumors of pelvic bone

Neuromuscular disturbances

• • • • • • • • • • • • • • • Fatigue (I)

b

Sleep disorders (P) Headache (P) Impaired mentation (I)

b

Lethargy (I)

b

Asterixis (I) Muscular irritability Peripheral neuropathy (I or P) Restless legs syndrome (I or P) Myoclonus (I) Seizures (I or P) Coma (I) Muscle cramps (P or D) Dialysis disequilibrium syndrome (D) Myopathy (P or D)

Cardiovascular and pulmonary disturbances

• • • • • • • • Arterial hypertension (I or P) Congestive heart failure or pulmonary edema (I) Pericarditis (I) Hypertrophic or dilated cardiomyopathy (I, P, or D) Uremic lung (I) Accelerated atherosclerosis (P or D) Hypotension and arrhythmias (D) Vascular calcification (P or D)

Correlation between the decline in kidney function,

and the increasing incidence of cardiovascular (CV) complications and death from CV disease 75.0

; , 60.0–74.9

; , 45.0–59.9

; , < 45

U.S. Renal Data System

showing increased likelihood of dying rather than starting dialysis or reaching stage 5 chronic kidney disease (CKD). Death , ESRD/D , event-free

HTN CKD DM MI

Traditional Risk Factors

Smoking Genetics

Non-traditional Risk Factors

Diabetes

Elevated IL-1, Il-6, TNF

a HTN Oxidation (OxLDL) Homocysteine Age Advanced glycation end-products Dyslipidemia Carbonyl stress

Fractures Cardiovascular disease in CKD

Low fetuin-A

Abnormal bone Abnormal mineral metabolism

Ischemic Vascular Disease

Any stage of CKD is a major risk factor for ischemic cardiovascular disease, including occlusive coronary, cerebrovascular, and peripheral vascular disease • • Traditional (classic) • hypertension, hypervolemia, dyslipidemia, sympathetic overactivity, and hyperhomocysteinemia Nontraditional (CKD-related) risk factors • anemia, hyperphosphatemia, hyperparathyroidism, sleep apnea, and generalized inflammation • circulating acute-phase reactants( cytokines and CRP • negative acute-phase reactants( serum albumin and fetuin)

Dermatologic disturbances

• • • • • • Pallor (I)

b

Hyperpigmentation (I, P, or D) Pruritus (P) Ecchymoses (I) Nephrogenic fibrosing dermopathy (D) Uremic frost (I)

Gastrointestinal disturbances

• • • • • • • Anorexia (I) Nausea and vomiting (I) Gastroenteritis (I) Peptic ulcer (I or P) Gastrointestinal bleeding (I, P, or D) Idiopathic ascites (D) Peritonitis (D)

Hematologic and immunologic disturbances

• • • • • • Anemia (I)

b

Lymphocytopenia (P) Bleeding diathesis (I or D)

b

Increased susceptibility to infection (I or P) Leukopenia (D) Thrombocytopenia (D)

Causes of Anemia in CKD •

Relative deficiency of erythropoietin

• Diminished red blood cell survival • Bleeding diathesis • Iron deficiency • Hyperparathyroidism/bone marrow fibrosis • "Chronic inflammation" • Folate or vitamin B 12 deficiency • Hemoglobinopathy • Comorbid conditions: hypo/hyperthyroidism, pregnancy, HIV-associated disease, autoimmune disease, immunosuppressive drugs

Abnormal Hemostasis

• • • • Patients with later stages of CKD may have a prolonged bleeding time : Decreased activity of platelet factor III , Abnormal platelet aggregation and adhesiveness Impaired prothrombin consumption. Interestingly, CKD patients also have a greater susceptibility to thromboembolism, especially if they have renal disease that includes nephrotic-range proteinuria. The latter condition results in hypoalbuminemia and renal loss of anticoagulant factors, which can lead to a thrombophilic state.

Abnormal Hemostasis: Treatment

• • • • • • Desmopressin (DDAVP) Cryoprecipitate IV conjugated estrogens Blood transfusions EPO therapy Optimal dialysis

Factors Suggesting CHRONICITY

Duration of symptoms / RF for months Absence of acute illness in face of very high urea and CREATININE Small kidneys on imaging Bone disease Neurological complications Skin / nail / eye changes

The Initial Assessment: Objectives

     

To confirm the primary renal diagnosis.

 

A. Conditions that can be arrested / reversed.

B. Conditions affecting dialysis / transplantation.



C. Conditions FORESEE. Genetic counseling / screening.

To establish CHRONICITY.

To identify reversible factors.

To detect INTERCURRENT illness.

To detect COMORBID factors.

To establish a baseline database.

UREMIA PATHOPHYSIOLOGY Na+ BALANCE H 2 O BALANCE K+ BALANCE H+ BALANCE Ca,Mg,,P,Vit D METABOLISM LOSS OF NEPHRONS ERYTHROPOIETIN CATABOLSIM OF PEPTIDES EXC.OF NITROGENOUS WASTES EXC. OF DRUGS

Approach To The Patient With CKD

      

Diagnosis: AETIOLOGY; Est.CHRONICITY

ASSESMENT of severity ASSESMENT of nutritional status Conservative management PREDIALYSIS / transplantation evaluation Dialysis access / HBV vaccination Dialysis / transplantation

Parameters To Follow

• • •

History :

symptoms of uremia

Physical:

wt/ supine - standing B.P

  Skin changes FUNDUS   Cardiac size / rub Neurological

Lab:

biochemistry / RADIOLOGY / others

Know about the varying natural history of different causes of CKD

Treatable Causes Of CKD

Systemic lupus ERYTHEMATOSIS Obstructive nephropathy ISCHEMIC nephropathy PYELONEPHRITIS GLOMERULONEPHRITIS HYPERTENSIVE NEPHROSCLEROSIS

Follow Up Assessment Objectives:

     MONITOR PROGRESS OF PRIMARY DISEASE & RESPONSE TO SPECIFIC TREATMENT MONITOR PROGRESS OF CKD & RESPONSE TO NONSPECIFIC TREATMENT TO WATCH OUT FOR INTERCURRENT ILLNESS TO DETECT COMPLICATIONS OF CKD TO FORESEE NEED FOR DIALYSIS / TRANSPLANTATION & PREPARE

AVOID AGGRAVATING RF CONSERVATIVE Mx OF CKD SLOW PROGRESSION OF RF TREAT. UREMIC SYMP

.

Measures To Avoid Aggravating RF

   

AVOID VOLUME DEPLETION / EXCESS CAREFUL DRUG USAGE AVOID ELECTROLYTE IMBALANCE AVOID PREGNANCIES IN HIGH RISK CASES



AVOID URINARY INSTRUMENTATION & CONTRAST STUDIES

Reversible Factors Aggravating CKD

       

CARDIAC FAILURE DRUGS:

NSAIDS, ACEI, AG, CONTRASTS, ETC

VOLUME DEPLETION HTN -

UNCONTROLLED / OVER TREATMENT

OBSTRUCTION INFECTION-

RENAL / EXTRA RENAL

CATABOLISM:

INFECTION, GI BLEED, SURGERY, ETC

ELECTROLYTE DISTURBANCES

Measures To Slow Progression Of RF

CONTROL HTN / CARDIAC RISK FACTORS DIETARY PROTEIN RESTRICTION SCREEN & TREAT UTI CONTROL HYPERPHOSPHATEMIA / HYPERURICEMIA TREAT HYPERLIPIDEMIA ACE INHIBITORS TREATMENT OF PRIMARY CAUSE GLYCEMIC CONTROL IN DIABETES

Stepped-care Parallels Impairment of GFR

Degree of CKD Action GFR Mild Moderate Severe 1,2,3,4 60-90 ml/min/1.73 m 2 30- 59 ml/min/1.73 m 2 15- 29 ml/min/1.73 m 2 Steps 1,2 Steps 1,2,3 Steps

Step 1 -

slow the progression of chronic kidney disease to end stage renal disease (ESRD)

Step 2 -

identify and treat co-morbid conditions (cardiovascular)

Step 3 -

identify and prevent complications of CKD (anemia, divalent ions, malnutrition)

Step 4 -

therapy prepare the patient mentally and physically for renal replacement

II III IV V

STAGE

I 0

CLASSIFICATION OF CKD - NKF

DESCRIPTION

WITH RISK FACTORS KIDNEY DAMAGE (WITH NORMAL OR  GFR) MILD MODERATE SEVERE KIDNEY FAILURE

GFR(ml/mt)

>90 >90 60-89 30-59 15-29 <15

Rationale for a stepped-care action plan

Degree of anemia parallels decline in GFR GFR (ref group GFR >80) Decrease in Hct (men) (women)

70-80 60-69 50-59 40-49 30-39 20-29 <20 -0.1% -0.1% -0.4% -0.3% -1.6% -2.6% -6.5% -.03% -0.3% -0.7% -2.2% -2.9% -3.8% -11.2% Kidney Int 2001; 59:725-731

Current Recommendations For Hypertension Control In CKD

Blood Pressure TARGETS HYPERTENSION WITHOUT CRF <130/85 HYPERTENSION WITH CRF& PROTEINURIA

<1G/DAY

HYPERTENSION WITH CRF& PROTEINURIA

>1G/DAY

<130/80 <125/75

AGEI/ARB RECOMMENDATIONS FOR USE IN CKD

 

ACE INHIBITOR AS FIRST LINE THEPRAPY

  IN TYPE-1 & TYPE-2 DM PATIENTS WITH MICRO/ MACROALBUMINURIA EVEN WITHOUT HTN/RF ALL PATIENTS WITH HTN AND/OR PROTEINURIA

ARB SAME INDICATIONS IF PATIENT INTOLERENT OF ACEI

     COMBINATION OF ACEI AND ARB MAY ALSO BE OF BENEFIT MONITOR CREATININE & K+ WEEKLY INITIALLY TOLERATE K + < 5.5. IF  >5.5mEq/L INSTITUTE LOW K + DOSE OF ACEI OR ARB DIET AND  TOLERATE RISE OF CREATININE OF < 20% ABOVE BASELINE AS LONG AS LEVEL PLATEUS IN 2-3 WEEKS DISCONTINUE DRUG IF EITHER K + >5.5 OR CRETININE>20% ABOVE BASELINE (CONSIDER RENAL ARTERY STENOSIS)

HTN CONTROL IN CKD

BP>15/10 >Goal, SCr <1.8

BP>15/10>Goal , SCr >1.8

ACEI/ATB+( Thiazide ) ACEI/ATB+( Loop diuretic ) BP still not at goal(130/80) Add Long Acting CCB( Pref -Non -DHP) Titrate to moderate dose BP still not at goal Baseline pulse>82 Add low dose ß or α+β Blocker Baseline pulse<82 Add other group CCB BP still not at goal Add long acting α-Blocker ?

Ref.to Nephrologist

Protein Restriction

INITIATE WHEN SERUM CREATININE IS >2.0 mg/dL in Men and >1.5 mg/dL in Women RESTRICT PROTEIN < 0.8G/Kg/DAY ENCOURAGE PROTEIN OF HIGH BIOLOGICAL VALUE MONITOR NUTRITIONAL PARAMETERS (ALBUMIN, PREALBUMIN)

Cardiovascular Risk Factors In CKD

• • • • • • SUSTAINED & REFRACTORY HTN CHRONIC ANEMIA DYSLIPIDEMIA  S.PHOSPHATE &VASCULAR CALCIFICATION INCREASED OXIDANT STRESS HYPERHOMOCYSTINEMIA

RECOMMENDATIONS FOR CVS RISK REDUCTION

AGGRESSIVE BP CONTROL (<130/80 ) MAXIMISE ACEI/ARB THERAPY DIURETICS AND SALT RESTRICTION NEEDED IN MOST ASSESS ANEMIA.

USE EPOITEN WHEN HB<10-11G% KEEP PHOSPHATE CONTROL(<5.5mg%). DIET ADVICE AND PHOSPHATE BINDERS ASSESS LIPID PROFILE AND USE DIET THERAPY, STATINS, FISH OIL SUPPLEMENTS TO KEEP LDL-C < 70-100mg% DAILY ANTIOXIDANT VITAMINS VIT-E (MIXTURE OF NATURAL ISOMERS) 400-800 IU,VIT-C 500mg, NATURAL



CAROTENE - UPTO 10,000IU SCREEN FOR HOMOCYSTENEMIA . IF ELEVATED ADVICE FOLIC ACID , B6 & B12

Principles Of Divalent Ion Management In CKD

• • • • CORRECTION OF HYPOCALCEMIA CORRECTION OF ACIDOSIS CORRECTION OF HYPERPHOPHATAEMIA MONITORING PTH LEVELS AND CONTROL OF RENAL OSTEODYSTROPHY

RECOMMENDATIONS FOR DIVALENT IONS MANAGEMENT HYPOCALCEMIA - MONITOR, ORAL CaCO3+/- CALCITRIOL ACIDOSIS - 1-4G OF NaHCO3 IF NOT CONTRAINDICATED BY HTN CONTROL AND FLUID BALANCE HYPERPHOSPHATAEMIA - MONITOR TARGET(<5.5mg%) DIET ADVICE, TO AVOID MILK & MILK PRODUCTS, PHOSPHATE BINDERS, BEST SEVELAMER - COSTLY, OTHERS CALCIUM CONTAINING - MONITOR S. CALCIUM, AVOID ALUMINIUM CONTAINING IN LONG TERM TRT.

PTH LEVELS GFR >50ml PTH UPPER NORMAL 20-50ml/mt <20ml/mt 1.0-1.5 TIMES 1.5-2.0 TIMES DIALYSIS 2.0-3.0 TIMES CORRECT HYPOCALCEMIA & HYPERPHOSPHATEMIA CALCITRIOL THERAPY

• • • • • • • • • •

10 A’s of CKD

Anemia A therosclerosis A nti-angiotensin therapy A lbumin A nions and Cations A rterial Blood Pressure Arterial Calcification A ccess A voidacne of Nephrotoxic Drugs A llograft

Treatment Of UREMIC Symptoms

• • • • • • • •

ITCHING: Protein Restriction Phosphate Restriction Antihistaminics Emollients UV Radiation Cholestyramine Boluso of Xylocaine Erythropoietin

• • • • • •

GI SYMPTOMS: Protein Restriction Correct Acidosis Small Frequent meals Antiemetics / Cisapride H2 Antagonists AL.OH Gel

• • • • • • • •

NEUROMUSCULAR: Protein Restriction Vitamins Exercise Muscle Relaxants Tranquilizers Quinine Anti-depressants Correction of Anemia

• • • • •

SKELETAL: Decrease & Bind Phosp Treat acidosis Calcium Supplements Clacitriol / 1 Alpha Treat severe hyperuricemia

• • •

ANEMIA Iron, Folate & B12 Erythropoietin Transfusion

Indications For Dialysis / TRANSPLANATATION

• • • • • •

INTRACTABLE UREMIC SYMPTOMS PERICARDITIS / PULMONARY OEDEMA OSTEO DYSTROPHY BLEEDING DIATHESIS ENCEPHALOPATHY / NEUROPATHY METABOLIC COMPLICATIONS (ESP. HYPERKALEMIA)

Renal replacement therapy

Hemodialysis Peritoneal dialysis Kidney transplant  Living donor  Cadaver transplant