Renal FailureBernito MashiloaneNephrologist in Private PracticePretoria

Outline of presentation

´ Anatomy of the kidney

´ Physiology

´ Presentation of kidney disease

´ Aetiology of kidney disease

´ Classification of CKD

´ Management and Prevention of Kidney Disease

´ Treatment Modalities

Functional unit of the kidneyNephron

Functions of the Kidneys

´ Regulation of blood volume and excess fluid

´ Regulation of Blood Pressure

´ Regulation of the PH of the blood

´ Production of Red Blood Cells

´ Activation of Vitamin D

´ Excretion of waste products and foreign substances

ISN/ERA-EDTA Statistics

´ Kidney disease is the 9th leading cause of death in the USA

´ An estimated 850million people worldwide have chronic kidney disease

´ 9 out of 10 people who have CKD do not know it

´ CKD is more common among women, but men with CKD are 50% more likely than women who have CKD to progress to ESRF

´ Some racial and ethnic groups are at a greater risk; AA,Asians, Hispanics,etc

ISN/ERA-EDTA Statistics

´ about 422 million people with diabetes mellitus

´ 42 million people with cancer

´ 36,7 million people with HIV/AIDS

´ there has been a 67% increase in deaths as result of kidney diseases in South Africa

´ the prevalence of kidney disease in the adult population in South Africa is 10 -12%

ISN/ERA-EDTA Statistics

´ about 10,5 million people need dialysis or a kidney transplant

´ Renal Replacement Therapy is not easily available to the majority due to cost or lack of resources

´ more than 13 million suffer AKI and about 33 % will progress to CKD or Kidney failure

´ The annual per-patient cost of dialysis is $88 195 in the USA and R70 - 80 000 in SA

South African Statistics

´ An estimate of more than 6 million south africans have CKD

´ The figure above is certainly higher in africans

´ Total number of patients on RRT as of December 2015 (prevalence of 189 /million population

´ The figures are increasing due to an increase in lifestyle diseases and HIV/AIDS

´ Diabetes Mellitus and Hypertension still remain the leading causes of CKD

Clinical presentation of Renal Disease´ Asymptomatic - Incidental finding

´ Non-specific symptoms - Myalgia, Arthralgia, Flu-like symptoms, LOA, Tiredness, Nausea or Vomiting

´ Swelling of the lower limbs or body, Periorbital swelling especially early mornings

´ Uncontrollable or elevated Blood Pressure

´ Recurrent urinary tract infections with or without urinary symptoms

´ Flank pains or vague abdominal pains

Presentation of Renal Failure

´ Acute Kidney Injury

´ Chronic Kidney Disease

´ Fulminant Kidney Failure

´ Acute on Chronic Kidney Disease

Acute Kidney Injury

´ An abrupt decrease in renal function sufficient to cause retention of metabolic waste such as urea and creatinine

´ Frequently results in the following:

´ Metabolic Acidosis

´ Hyperkalaemia

´ Disturbance in body fluid homeostasis

´ Secondary effects on other organ systems

Causes of Acute Kidney Injury

´ Acute Tubular Necrosis

´ Severe or Sudden Dehydration

´ Toxic kidney injury from poisons or certain medications

´ Autoimmune kidney diseases - Acute Nephrotic syndrome, Interstitial nephritis

´ Urinary Tract Obstruction

Causes of Acute Kidney Injury

´ Community acquired - Prerenal (70 %). Interruption of blood supply from severe injury or illness

´ Hospital acquired - ATN (30-50 %) - ischemia, nephrotoxic injury, inflammation, infection, toxins MR 50 - 70%

´ Post Renal - Obstuctive uropathy. Enlarged prostate, tumor or kidney stones

Investigations

´ Urinalysis

´ Routine Bloods

´ Special Blood tests

´ Imaging – Pelvis / Abdominal ultrasound

´ Kidney Biopsy – Gold standard

Kidney ‘Troponins’(Bio-markers)´ NGAL - neutrophil gelatinase-associated lipocalin

´ NAG - N-acetyl-B-D-glucosaminidase

´ KIM-1 Molecule

´ Cystatin - C

´ IL-18

´ L - FABP - liver fatty acid-binding protein

´ IGFBP7 - insulin-like growth factor binding protein 7

Treatment of AKI

´ Treatment of the underlying cause

´ Adequate hydration

´ Diuresis if necessary

´ Dialysis - hemodialysis or peritoneal dialysis

´ Renal transplant

Indications for initiating RRT

´ Refractory fluid overload

´ Hyperkalaemia resistant to medical therapy

´ Intractable Metabolic acidosis

´ Azotemia - high urea level

´ Signs of uraemia - pericarditis, neuropathy, encephalopathy, melaena

´ Severe dysnatremias - hypo/hypernatremia

´ Hyperthermia

´ Overdose with a dialysable drug/toxin

Nephritic syndrome

´ Inflammatory condition

´ Active urinary sediment - red cells, granular casts, red cell casts

´ Variable degree of proteinuria (< 3,5 g/day)

Nephrotic Syndrome

´ No inflammation

´ Bland urinary sediment - no cells, fatty or hyaline casts

´ Nephrotic range proteinuria - > 3,5 g/day)

´ Triad - proteinuria, hyperlipidemia and oedema

Chronic Kidney Disease

´ eGFR < 60 ml/min for 3 months or more

´ A progrèssive and irreversible deterioration in Renal function

´ Results in accumulation of waste products, organ dysfunction, fluid imbalance

Risk Factors for CKD

´ Diabetes mellitus

´ Hypertension

´ Previous kidney disease

´ Smoking history

´ Family history of genetic kidney disease

Causes of Renal Failure

´ Vascular - Vasculitis, TTP/HUS, Malignant HPT, RAS

´ Glomerular - GN, Vasculitis, DN, Amyloidosis, IGAN,SLE

´ Interstitial - AIN, ATN

´ Tubulointerstitial diseases – PCKD, Other Cystic ds

other causes

´ NSAIDS - OTC, used for minor ailments

´ Aminoglycosides - Amikacin, Streptomycin, Gentamycin

´ Chemo and Radiotherapy - results in tumor lysis syndrome

´ Traditional medicine and herbs - Chinese herbs - Aristolochic acid, Moringa, Lerumo la madi, Imbiza

Nephrotoxic agents

´ Antibiotics - Aminoglycosides, Amphotericin B, Cephalosporins

´ Analgesic Agents - Non-Steroidal Anti-inflammatory

´ AntiViral Agents - Acyclovir, TDF, PI

´ Antihypertensive Agents – ACE-I, ARB

´ Chemotherapeutic Agents – Cyclosporine, Cisplatin

´ Traditional medicines – Aristolochic acid

´ Pre-emptive dialysis : eGFR 10 - 14 ml/min

´ Established symptoms : eGFR 5 - 7 ml/min

´ Recommendation : eGFR 5 - 9 ml/min

Early vs Late dialysis

´ Considerable variation in the timing of maintenance dialysis in patients with ESRF

´ There is a worldwide trend towards early initiation

´ Planned early dialysis in patients with ESRF not associated with an improvement in survival or clinical outcomes

´ A study by X Yang et al (China) :

´ Early initiation of dialysis in critically ill patients did not result in reduced mortality

´ No improvement in secondary outcomes

Cardiovascular complications of Kidney Failure

´ A leading cause of mortality in CKD patients

´ Cause of IHD, CCF and Hypertension

´ Increased risk due to shared risk factors with CKD risk factors

´ CKD related factors include anaemia, hyperphosphatemia, hyperparathyroidism, sleep apnoea and a generalised state of inflammation

´ Microalbuminuria is a major risk factor

Kidney Diseases in women

´ About 12 - 14 % of women worldwide are affected by chronic kidney disease

´ CKD is the 8th leading cause of death

´ Estimated that 600 000 deaths annually from CKD due to lack of access, cultural or traditional dictates, discrimination

´ About 16 % of women are more likely to have CKD stages 1 -4 than their male counterparts

Complications of kidney disease in women

´ Irregular menstruation - Excessive bleeding, missed periods, early onset of menopause

´ Sexual dysfunction - Hormonal Imbalances, presence of Diabetes Mellitus, Medications, Pregnancy

´ Pregnancy - Miscarriages, Pre-term delivery, IUGR, rapid deterioration of kidney function

´ Bone disease - Osteoporosis, accelerated decrease in bone density

´ Major Depression - Chronic illness, occurs in about 1/4 of patients on dialysis

HIV and Kidney Disease

´ HIV is the 7th leading cause of ESRF

´ May present with either AKI or CKD

´ Direct cytotoxic effects - HIVAN (Incidence is reduced since the roll-out of HAART)

´ Other lesions include FSGS,HIVICK, TMA, TTP/HUS

´ Associated with adverse outcomes

Risk factors for kidney disease in people living with HIV´ Poorly controlled HIV infection - low CD4 count , High Viral load

´ Co-Infection with Hepatitis B or C infection

´ Antiretroviral agents used - TDF, PI

´ Elderly patients

´ Presence of co-morbid conditions

´ Patients with pre-existing kidney disease

´ Female gender

Non-diabetic kidney disease

´ Patients of african-american ancestry, MYH9 gene located near the APOL-1 gene on chromosome 22

´ With concomitant use of nephrotoxic agents

´ The use of TDF or PI alone or in combination

´ A CD 4 count of < 200 cells/m3 (AIDS)

´ Commonest histopathological lesion - FSGS

Prevention of Renal Failure

´ Identify patients at risk of CKD at an early stage and treat aggressively

´ Appropriate detection and treatment of various glomerulonephritidis

´ Control of Diabetes Mellitus,Hypertension, Hyperlipidemia and other associated risk factors

´ Cautious use or avoidance of nephrotoxic agents

´ Early detection of polycystic disease and its treatment

Non-pharmacological Management

´ Consider adequate hydration and use of allopurinol in patients receiving chemotherapy

´ Avoid nephrotoxins, OTC and contrast agent administration

´ Dose-adjustments of certain drugs when necessary

´ Optimal fluid administration

´ Lifestyle modifications and dietary restrictions

´ Cessation of smoking and reduction of alcohol consumption

´ Aerobic exercise and weight loss if obese or overweight

´ Referral to a dietitian for lifestyle modification and dietary restrictions

´ Mitigate associated cardiovascular risk factors

Contrast-Associated AKI

´ Pre-existing renal insufficiency

´ Diabetes Mellitus

´ Proteinuria

´ Intravascular volume depletion

´ Reduced Cardiac Output

´ Concomitant Nephrotoxins

Pathophysiology of CAAKI

´ Intra-renal Vasoconstriction

´ Altered Blood rheology

´ Osmotic load

´ Generation of ROS

´ Direct Cytotoxicity

´ Medullary Hypoxia

´ Acute Kidney Injury

Renal Replacement Therapies´ Peritoneal Dialysis : CAPD, APD, CCPD

´ Hemodialysis : In-center vs Home Hemodialysis

´ Kidney Transplanatation : Cadaver, Living-related and Living Non-Related kidney transplant

´ Conservative management - Palliation

Kidney Transplant

´ Definite treatment for patients with Renal Failure

´ Deceased donation or Live Donation (Related or NRLD)

´ Scarcity of donations - Beliefs, Chronic conditions, HIV

´ Long waiting times

´ Associated complications - rejection, Infections, Malignancy, CVD

Principal targets for renal protection

´ Attainment of blood pressure goal

´ In proteinuric patients, attainment of proteinuria goal

´ Reduction in urinary protein excretion

´ Use of ACE-I or ARB’s

´ Avoidance of nephrotoxic agents

other targets

´ reduction of protein intake to less than 1g/kg/day

´ cessation of smoking

´ treatment of metabolic acidosis with supplemental bicarbonate

´ glycemic control to delay progression of proteinuria and CKD

´ maintaining regular exercise regime

References :

´ NEJM 2010, 363; 609 - 613

´ SA RENAL SOCIETY, Annual Report 2015

´ American Kidney Fund

´ Australia / New Zealand RCT

´ CJASN 6; 1222 - 1228, 2011

´ NDT 2011 , 26; 2082 - 2086

´ Guidelines on Chronic c Hemodialysis, 2009; DOH

´ SARS Guidelines