1. UNUSUAL CASE OF ARF Dr SAAD AL SHOHAIB KAUH

2. CASE PRESENTATION 58 Y old Yemeni male Diabetic for 5 years with no obvious diabetic complications particularly no retinopathy Admitted with fever and pain in both legs for 4 days

3. CASE PRESENTATION He had no other symptoms particularly no dyspnea cough or chest pain He had no GI symptoms and no urinary symptoms

4. CASE PRESENTATION P.M.H Hypertension for 5 years on enalapril 5 mg once daily No history of IHD

5. Case presentation Social history Non smoker married 3 children

6. Case presentation On examination He looked well B P 135/80 Temp 38.5 pulse 90/min regular JVP normal chest clear CVS normal Abdomen normal

7. Case presentation Cellulitis both legs extending from ankles to both knees No obvious collection Good peripheral pulses No evidence of peripheral nueropathy

8. Case presentation Lab work WBC 17 Mainly nuetrophils Hb 13.1 Na 138 K 4.1 urea 18 mmol/l Cr 212 umol/l Ca 2.1 mmol/l P 1.6mmol/l Urinalysis proteinuria no hemturia no casts LFT normal

9. Case presentation Lab data U/S normal size kidneys C 3 and C4 normal ANA negative Hepatitis screen negative

10. Course in hospital Started on ceftrixone and clindamycin with his usual medications His temprature subsided and cellulitis improved

11. Course in hospital His urine output had been maintained within normal range but his renal function got worse and finally his creatinine reached 1100 umol/l and urea 45 mmol/l K 5.5 but no fluid over load Dialysis was started

12. Diff diagnosis Post infectious GN Drug induced Pre existing diabetic nephropathy got worse with sepsis

13. Kidney biopsy Normal glomeruli No interstilal infeltrate

14. Course in hospital He was dialysed for 10 days then his renal function stated to improve and creatinine decreased and reached normal value tow weeks after stopping dialysis At that time he became polyuric for one week He was sent home in good medical condition

15. Post infectious G N Immune complex nephritis can follow any bacterial viral fungal or parasitic infections Can follow infected shunts and endocardits May complicate deep abscesses Usually present 3 weeks post infection

18. Post infectious G N Hematuria edema Oliguria hypertension Fever Uncommonly ARF requiring dialysis

19. NSAID HEMODYNAMICALLY-MEDIATED ACUTE RENAL FAILURE Although renal prostaglandins are primarily vasodilators, they do not play a major role in the regulation of renal hemodynamics in normal subjects the release of these hormones (particularly prostacyclin and prostaglandin E2) is increased by underlying glomerular disease, renal insufficiency, hypercalcemia, and the vasoconstrictors angiotensin

20. NSAID HEMODYNAMICALLY-MEDIATED ACUTE RENAL FAILURE Inhibition of prostaglandin synthesis with an NSAID in any of the above settings can lead to reversible renal ischemia, a decline in glomerular hydraulic pressure and ARF

22. ACUTE INTERSTITIAL NEPHRITIS Any drug can induce AIN however it is seen more with antibiotics Affected patients typically present with hematuria, pyuria, white cell casts, proteinuria, and an acute rise in the plasma creatinine concentration. Fever, rash, eosinophilia, eosinophiluria – can be seen but not always present. Spontaneous recovery generally occurs within days weeks to a few months after therapy is discontinued

29. Acute interstitial nephritis The clinical picture is usually suggestive however the diagnosis is confirmed by renal biopsy Gallium scan may be helpful High dose steroid is useful to speed up recovery

30. ATN Any pre renal cause can lead to ATN if not corrected on time The renal medulla is very sensitive to ischemia particularly in old dehydrated diabetic patients or those with CHF or liver cirrhosis Nephrotoxic drugs would aggravate renal damage

31. ATN Mostly seen in the ICU setting It is a clinical diagnosis Biopsy is usually not indcated

34. ATN Fluid challenge is an important therapeutic and diagnostic approach Examination of the urine Na and osmolarity are very important The condition is potentially reversible but the mortality is still 50% since it happens in very sick patients

35. Diabetic nephropathy Diabetes is common in Saudi Arabia This mainly related to genetic factors as well as the life style 40% of patients with ERSD are diabetics

36. Dialysis in Saudi Arabia There are 6700 patients on dialysis in Saudi Arabia There is 130 haemodialysis centres in Saudi Arabia The incidence of hepatitis B is 6.7%and 50% for HCV SCOT data Saudi J kid 2001 12 (3)

37. Diabetic nephropathy Common problem 30 - 40% of dialysis patients are diabetics Long standing diabetes Genetic predisposition hypertension poor glycemic control are important risk factors Strongly associated with retinopathy

38. Diabetic nephropathy stages 1. Increased GFR and hyperfiltration 2. Normal GFR and mild mesangial expansion 3. Microalbumiuria 4. Overt proteinuria 5. CRF

39. Diabetic nephropathy diagnosis Clinical diagnosis Long standing D M particularly in type 1 Proteinuria or microalbumiuria Retinopathy Inactive urinary sediment Normal sized kidneys

40. Diabetic nephropathy Microalbumiuria is a sign of cariovscular disease and is a very important finding since interference with strict glycemic control and ACE inhibitors is important Strict glycemic control can reverse glomerular changes Blood pressure control is vital and the ACE inhibitor dose should be titrated to the degree of proteinuria

41. The Kidney’s

43. Type 1 Strict glycaemic control can decrease the nephropathy and progression of rena disese

44. It has been suggested that 25 to 45 percent of these patients will, during their lifetime, develop clinically evident disease Type one DM

45. Strct blood pressure control is very imprtant Genetic factors play major role in diabetic nephropathy Most patients have retinopathy Most are asymptomatic

46. Urinary albumin excretion Mogensen CE et al. Lancet 1995; 346: 1080–1084 Clinical proteinuria >300 mg/24 hrs (>200 µg/min) Microalbuminuria 30–300 mg/24 hrs (20–200 µg/min) Normal excretion <30 mg/24 hrs (<20 µg/min)

47. Microalbuminuria: Prevalence and predictive power in diabetics Type 1 diabetes Prevalence: 50% Predictive value for the development of nephropathy: 75% Type 2 diabetes Prevalence: 25–60% (depending on ethnic origin) Predictive value for the development of nephropathy: 25% Savage MW et al. Br J Hosp Med 1995; 54: 429–435 Viberti GC et al. In: International Textbook of Diabetic Medicine, 1992

48. Serum creatinine level of 1.4 mg/dl: What is the renal function? Serum creatinine (mg/dl) 12 10 8 6 4 2 0 Large muscular male Normal male Small female 120603015 Fraction of normal renal function (%) Sica DA. Unpublished data 10050250 GFR (ml/min)

49. ACE inhibitors in hypertension and heart failure In hypertension, ACE inhibitors Lower blood pressure Reduce the progression of end-organ damage In heart failure, ACE inhibitors Improve cardiovascular hemodynamics Improve symptomatolgy and exercise capacity Decrease morbidity and mortality

50. ACE inhibitors and renal impairment: Considerations Occasional cases of renal impairment and hyperkalemia have been reported with ACE inhibitors Dose modifications are a consideration in patients with renal impairment (except for fosinopril) ACE inhibitors show renoprotective effects over and above blood pressure control ACE inhibitors

51. Renoprotection: ACE inhibitors vs. other antihypertensives Calcium antagonistsACE inhibitors Diuretics and/or  - blockers Urinary protein Mean systemic blood pressure 0–10–20–30–40–50 Decrease from baseline (%) Böhlen L et al. Am J Hypertens 1994; 7: 84S–92S

52. ACE inhibitors are renoprotective Patients with type 2 diabetes Patients with type 1 diabetes Non-diabetic patients with nephropathy Non-diabetic patients with hypertension and nephropathy Non-diabetic hypertensive patients without pre-existing nephropathy ACE inhibitors have demonstrated renoprotective potential in:

53. ACE inhibition: Renoprotection in type 2 diabetes Initial value of reciprocal creatinine (%) 105 100 95 90 85 80 0123456701234567 Treatment (years) Ravid M et al. Arch Intern Med 1996; 156: 286–289 ACE inhibitor (years 1–5) and placebo (years 6 and 7) ACE inhibitor (years 1–7) Placebo (years 1–5) and ACE inhibitor (years 6 and 7) Placebo (years 1–7)

54. ACE inhibition: Renoprotection in type 1 diabetes Placebo Captopril 50 40 30 20 10 0 Died or needed dialysis or transplantation (%) 0123401234 Follow-up (years) Placebon=2021981921861711211005926 Captopriln=2072072042011951401036437 Lewis EJ et al. N Engl J Med 1993; 329: 1456–1462 p=0.006

55. ACE inhibitors are renoprotective Patients with type 2 diabetes Patients with type 1 diabetes Non-diabetic patients with nephropathy Non-diabetic patients with hypertension and nephropathy Non-diabetic hypertensive patients without pre-existing nephropathy ACE inhibitors have demonstrated renoprotective potential in:

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