renal failure · ´ imaging – pelvis / abdominal ultrasound ´ kidney biopsy – gold standard....
TRANSCRIPT
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