1. Renal Disease Chronic Kidney Disease GP Management Ross Bills

2. Prevalence  1.7 million Australians with Stage three chronic kidney disease  1 in 7 Australians has chronic kidney disease  Often asymptomatic, 80-90% of cases unrecognised and untreated  10-20 fold increase in risk of death due to cardiovascular events  1 nephrologist per 95,000 adult Australians

3. Diagnostic criteria Chronic kidney disease (CKD) is defined as: A glomerular filtration rate (GFR) less than 60 mL/min/1.73m 2 that is present for 3 or more months, with or without, evidence of kidney damage OR Evidence of kidney damage (with or without decreased GFR) that is present for > 3 months, as evidenced by any of the following Microalbuminuria Proteinuria glomerular haematuria pathologic abnormalities (e.g. abnormal renal biopsy) anatomical abnormalities (e.g. scarring seen on imaging or polycystic kidneys).

4. GP Role  early detection of CKD  instituting therapies which will slow or prevent progression to kidney failure  assessing and modifying cardiovascular risk factors  avoiding nephrotoxic drugs

5. eGFR The MDRD (abbreviated) equation for use with SI units is: GFR = 186 x {[S Cr (umol/L)/88.4] -1.154 } x (age) -0.203 x (0.742 if female)

6. Pathologies Easiest to think of –Pre-renal Hypertension Renal artery stenosis Phaeochromocytoma Multiple organ failure/shock –Renal Glomerulopathies: acute and chronic, infective, autoimmune, protein deposition (amyloidosis), chemical (lead), drug related Diabetes nephropathy Mass - tumour (adenocarcinoma commonest adults, nephroblastoma children), polycystic disease –Post-renal Calculi and other obstructive (analgesic nephropathy) Strictures ureter intrinsic and extrinsic

7. Risk Factors  Smoking  Diabetes  Hypertension  Age > 50 years  Family History of Kidney Disease  ATSI Patients

8. The Kidney Screen  Simple screen at presentation.  If risk factors present: Check BP Dipstick for protein Creatinine level for eGFR  If eGFR > 60, normal BP, No proteinuria, low risk. Review opportunistically.  Caution if other evidence of renal disease - haematuria, casts etc.

9. eGFR  The new measure of renal function, using prediction equations based on age, sex and creatinine clearance  Abbreviated MDRD Formula GFR = 186 × (S CR + 88.4) -1.154 × AGE -0.203 Female: multiply result by 0.742) When used in Afro-Americans the result should be multiplied by 1.21

10. eGFR 2  Clinical situations where eGFR results may be unreliable and/or misleading: Acute changes in kidney function (eg. acute kidney failure) Dialysis-dependent patients Exceptional dietary intake (eg. vegetarian diet, high protein diet, creatine supplements) Extremes of body size Diseases of skeletal muscle, paraplegia, those with high muscle mass and amputees Children under the age of 18 years Severe liver disease present eGFR values above 60 mL/min/1.73m2

11. eGFR 3  eGFR has not been validated or shown to have acceptable accuracy in: Aboriginal and Torres Strait Islander peoples Asian populations (including Japanese, Chinese and Vietnamese) Maori and Pacific Islander peoples Calculations for drug dosing  In these clinical situations listed, an alternative method of estimating kidney function should be performed.

12. Presentations  Stage 1 - Kidney damage, no loss of function  Stage 2 - Kidney damage with mild loss of function There may be no clinical diagnostic features other than mild impairment of Creatinine Clearance/eGFR (eGFR >60) Address co-morbidity: BP Lipids Diabetes Smoking Weight Exercise

13. Signs/Symptoms Stage I - II  Bugger all

14. Complications Stage I - II  Usually just hypertension if anything

15. Presentations 2  Stage 3 - moderate loss kidney function  eGFR 30-59 Look at modifiable risk factors Monitor eGFR (three monthly Consider referral to nephrologist

16. Stage III Clinical Findings  Nil or  nocturia  mild malaise  anorexia

17. Stage III Complications Hypertension Hyperparathyroidism Renal Osteodystrophy Anaemia Sleep Apnoea Restless legs CVD Malnutrition

18. Management Stage III  Diagnosis  Cardiac and kidney risk factor modification  Treat complications

19. Modifiable Risk Factors Avoid nephrotoxic drugs Consider ACE Medication (inhibitors/blockers) - (antiproteinuric effect) Address co-morbidities: BP Lipids Diabetes Smoking Weight Exercise Correct: Anaemia Acidosis Hyperparathyroidism Ensure appropriate drug doses for renal function

20. Non-modifiable Risk Factors  Can’t change: Age > 50 years Family History of renal disease ATSI heritage

21. Presentations 3  Stage 4 - severe decrease renal function  eGFR 15-29  Needs referral to nephrologist. Considering dialysis, shunt for access, education and transplantation

22. Stage IV Clinical Findings  Nil or nocturia,  malaise  anorexia  nausea  pruritis  restless legs  dyspnoea

23. Stage IV Complications Hypertension Hyperparathyroidism Renal Osteodystrophy Anaemia Sleep Apnoea CVD Malnutrition Hyperphosphataemia Acidosis Hyperkalaemia

24. Management Stage IV  Diagnosis  Cardiac and kidney risk factor modification  Treat complications  Dialysis education  Dialysis access surgery

25. Referral to Nephrologist  Indications for Referral to a Nephrologist eGFR <30 mL/min/1.73 m2 Rapidly declining kidney function (>15% in eGFR over 3 months irrespective of baseline level) Proteinuria >1g/24 hrs Glomerular haematuria Kidney disease and hypertension that proves difficult to control Diabetes and eGFR <60 mL/min/1.73 m2

26. Presentation 4  Stage V  End stage kidney failure  eGFR < 15  Referral/dialysis or transplantation

27. Stage V Clinical Findings  nocturia  mild malaise  anorexia  nausea  vomiting  pruritis  restless legs  dyspnoea

28. Management Stage V  Dialysis or transplantation (or conservative medical management)  Cardiac and kidney risk factor modification

29. Stage V Complications Hypertension Hyperparathyroidism Renal Osteodystrophy Anaemia Sleep Apnoea CVD Malnutrition Hyperphosphataemia Acidosis Hyperkalaemia Pericarditis GIT bleeding Encephalopathy Neuropathy

30. General Management  Early Detection  Appropriate referral  Modify risk factors  Treat associated complications  Treat associated co-morbidities

31. Investigations eGFR is a good start point Look for other co-morbidities (McGovern’s Law) Basics like BP, weight, cardiovascular assessment, BSL, urine protein assessment are useful as early indicators Urea - imprecise, often elevated in dehydration/fasting 24 hour urine protein/creatinine clearance useful Imaging: Ultrasound (macroscopic imaging) CT/MRI IVP - with caution in patients with impaired renal function (calculus) Cystoscopy/Urethroscopy Intervention: Biopsy for tissue diagnosis of pathology

32. McGovern’s Law  Number of conditions found at autopsy that may account for the death of the patient equals the age of the patient (years) divided by 10, plus one.  For a sixty year old, 6 + 1 = 7.

33. Treating Hypertension Blood pressure reduction CKD can cause and aggravate hypertension, and hypertension can contribute to the progression of CKD. Reducing blood pressure to target levels is one of the most important goals in management of CKD. Angiotensin converting enzyme inhibitors (ACEI) are currently recommended as first line therapy, but angiotensin receptor blockers (ARB) may provide similar kidney protection. Hypertension may be difficult to control and multiple (i.e. 3 - 4) medications are frequently required.

34. Antiproteinuric Agents Antiproteinuric agents ACEI and ARB are more effective than other anti-hypertensive agents in reducing protein excretion and in slowing kidney function decline. However, these medications can cause an increase in serum creatinine when treatment is initiated. If the increase in creatinine is less than 30% and stabilises within two months of starting therapy, medication should be continued. If the rise in creatinine level exceeds 30% above the baseline value, medication should be ceased and consideration be given to investigating the possibility of bilateral renal artery stenosis.

35. Lipids  Lipid-lowering treatments The use of statins in people with CKD, who have hypercholesterolaemia, slows kidney failure progression.

36. Blood Glucose Levels  Glycaemic control Intensive blood sugar control significantly reduces the risk of developing CKD in the early stages.  However, the benefits in established CKD are not known.

37. Anaemia  Correction of anaemia There is some evidence that correction of anaemia may slow progression of CKD. Although this has not been proven, people certainly feel better. Hb < 110 g/dL Correct iron deficiency/diet Erythropoietin? GIT loss?

38. Lifestyle  Smoking  Nutrition  Alcohol  Physical activity Cease smoking Dietary salt intake < 1 mmol/kg/day < 2 standard glasses alcohol/day > 30 mins/day physical activity BMI < 25 kg/m 2 WC < 102 cm (male), < 88 cm (female)

39. Hypertension  Treatment goals: < 130/ 80 mmHg 1g/day ACEI and/or ARB first-line lifestyle modification

40. Proteinuria  > 50% reduction of baseline value ACEI and/or ARB first-line

41. Cholesterol  Total Cholesterol < 4.0 mmol  LDL Cholesterol < 2.5 mmol/L Dietary advice Statins

42. Blood Glucose Level  Pre-prandial BSL 4.4 - 6.7 mmol  HbA1c < 7.0% Lifestyle modification Oral hypoglycaemics Insulin

43. Acidosis  Acidosis  HCO3 < 22 mmol/L  Sodium Bicarbonate tablets

44. Dietary Protein Intake  0.7 - 1.0 g/Kg body weight/day  Dietary advice, low protein diet as indicated

45. Hyperkalaemia  K+ > 6.0 mml/L Dietary advice Diuretics Resonium??? Cease ACEI/ARB if K + persistently > 6.0 mmol/L

46. Hyperparathyroidism  PO 4 1.6 mmol/L  PTH 2-5 x upper limit of normal  Calcitriol  Phosphate binders (calcium carbonate, aluminium hydroxide, magnesium trisilicate, sevelamer)  Cinacalcet

47. Malnutrition  Albumen < 35 g/L  Dietary advice

48. Sleep apnoea  Prevent apnoeac episodes  Manage condition: Weight reduction Avoid CNS depressants CPAP therapy (if obstructive pattern

49. Restless legs  Correct iron deficiency  Dopaminergic agents  Herbal options: Crampeze,  Exercise/stretches

50. Drugs to reduce or cease Acetazolamide Acyclovir Colchicine Digoxin Gabapentin Lithium metformin (significantly increased risk of lactic acidosis when GFR < 50 mL/min/1.73m 2 ) Sotalol sulphonylureas.

51. Drugs affecting renal function in CKD NSAIDs and COX-2 inhibitors ACE inhibitors and angiotensin II receptor antagonists beware, especially, the 'triple whammy' of NSAID/COX-2 inhibitor, ACE inhibitor and diuretic radiographic contrast agents Aminoglycosides lithium.

52. Renal osteodystrophy Renal osteodystrophy is multifactorial. The aetiology includes: Reduced production of the active form of vitamin D by the diseased kidneys. A drop in vitamin D reduces the intestinal absorption of calcium and causes a fall in the blood level of calcium. If calcium levels in the blood become too low, parathyroid hormone (PTH) production is increased. PTH tries to keep the calcium level in the blood normal by: –increasing calcium resorption from bones –increasing production of vitamin D by the kidney in an attempt to increase calcium absorption from the intestine –increasing resorption of calcium by the kidneys to reduce renal losses. –Vitamin D and PTH usually work together to maintain calcium homeostasis. However, in CKD, the kidneys have a reduced ability to produce the active form of vitamin D and the hypocalcaemia that develops cannot be corrected. This causes PTH levels to rise still further. Because the intestinal absorption of calcium is impaired, the net result is resorption of calcium from the bones.