The Other Side Of A Coin 1

The Other Side of A Coin Wong KW 30 January 2008

The usual scenario:
55 year-old
Known diabetic 15 years
Private GP follow-up: irregular
No blood tests done before
Unwell past few weeks
Admitted with urea 40mmol/l, Creatinine 450umol/l, proteinuria, Hb 8.2g/dL
Advanced diabetic retinopathy
Ultrasound no obstruction
Diagnosis: advanced chronic kidney disease secondary to diabetic nephropathy

Case 1
68 year-old gentleman
Multiple medical problems:
Diabetes mellitus – 20 years
Hypertension – 10 years
Ischemic heart disease – Old MI with PTCA done 1995 (LAD)
Admitted to IJN April 2005 for congestive cardiac failure

Case 1
Referred for worsening renal function
No history of renal disease before
Normal baseline renal function
History of bilateral lower limb swelling for over a week prior to admission
Started on diuretic
Other drugs: valsartan, aspirin, simvastatin, gliclazide

Case 1
BP 173/86, pulse 97
Afebrile
Bibasal crackles
Pedal oedema +++
Urine Protein +, RBC 3-5hpf, no cast

Case 1 474 259 248 186 133 117 Creatinine 21.7 32.2 29.5 27.5 20.2 15.3 Urea 06/05/05 27/04/05 26/04/05 22/04/05 19/04/05 17/04/05

Case 1
Investigations: ANCA negative, ANA negative, Hepatitis status negative
Ultrasound – normal kidneys, no obstruction
24 hour urine protein: 2.9g/d

Case 1 - differentials?
Overdiuresis?
Acute interstitial nephritis? (frusemide)
Drug-induced? (valsartan)
Primary GN?
Progression of diabetic nephropathy?

Case 1
Worsening renal function
Hemodialysis started
Started on steroid – started on 5 th May 2005
Last HD 10 th May 2005
Renal biopsy

Case 1
Renal biopsy done on 12 May 2005 –
2 cores of renal corticomedullary tissue – 17 glomeruli. Mild expansion of mesangium, otherwise normal glomeruli
No sclerotic, proliferative or necrotizing lesions
Interstitium oedematous and shows several collections of lymphocytes, plasma cells and a few eosionophils

Case 1
Diagnosis – interstitial nephritis, consistent with a hypersensitivity aetiology
Started on steroid for two weeks, then tapered off

Case 1

Acute interstitial nephritis
Drugs (71%)
Infection-related (15%)
Idiopathic (8%)
Sarcoidosis (1 %)
NSAIDs - including selective COX-2 inhibitors
Penicillins and cephalosporins
Rifampicin
Sulfonamides, including bactrim and frusemide, bumetinide, thiazide-type diuretics
Ciprofloxacin
Cimetidine
Allopurinol
Proton pump inhibitors
Indinavir
5-aminosalicylates

Case 2
62 year-old lady
Diabetes mellitus
Hypertension
No other medical history - no urine dipstick done past 5 years
On metformin, lovastatin, chlorothiazide, aspirin, perindopril
Presented with bilateral lower limb rash – purpuric rash then blister both lower limbs for 2 weeks
Started at ankles, spread to knees

Case 2
Did take some traditional medicines for past 1 month
No fever, URTI
No oral/genital ulcers
OE – lower limbs superficial ulcers with necrotic centre

Case 2
Referred for urine blood 2+, protein 2+
Dysmorphic cells seen
Nephrotic syndrome :
24 hour urine protein 5.05g
Serum albumin 27g/l
Oedema
ANA, hepatitis status, RF – negative
C3C4 normal
Renal function NORMAL

Case 2 - Differential diagnosis?
Diabetic nephropathy
Henoch Scholein Purpura
Systemic vasculitis
Membranous GN
Minimal change disease
FSGS

Case 2
Renal biopsy:
35 glomeruli – 3 global sclerosed, a few show segmental mild endocapillary proliferation with a few neutrophils, focal segmental sclerosis noted, remaining glomeruli show mild mesangial expansion and mild proliferation of mesangial cells
No significant inflammatory cell infiltration
Immunofluorescence – Mesangial IgA(3+)
Summary: IgA nephropathy

Case 2
Interestingly:
Skin biopsy – perivascular infiltration by neutrophils and in areas, cells are seen invading the walls
Immunofluorescence stains are negative
Compatible with leucocytoclastic vasculitis

Case Summary
Case 1: diabetic patient with acute renal failure due to AIN secondary to drug
Case 2: diabetic patient with nephrotic syndrome due to primary glomerular disease – HSP

One of the commonest complications of DM
20% of patients with DM >20years
Leading cause of ESRD in many countries

14 th Report of The Malaysian Dialysis & Transplant Registry 2006 1 1 1 1 1 1 1 1 1 1 % Others 6 7 7 7 7 9 12 11 8 9 % Hypertension 0 0 0 0 0 1 0 1 0 0 % Toxic Nephropathy 2 2 2 3 3 3 3 4 5 5 % Obstructive Nephropathy 1 1 1 1 1 2 1 1 1 2 % Polycystic kidney 1 1 1 1 1 1 2 2 1 1 % SLE 3 5 4 5 6 6 9 10 10 13 % GN 57 55 54 53 50 46 45 41 41 36 % Diabetes Mellitus 27 26 28 28 30 30 28 29 32 33 % Unknown cause 3152 3054 2858 2597 2348 2085 1840 1544 1152 1136 New Dialysis patients 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 Year

Not all diabetic patients have diabetic nephropathy
Type I DM - >10 years, retinopathy, neuropathy – usually diabetic nephropathy
Anderson AR, Sandahl Christiansen J, Andersen JK, Kreiner,S, Deckert T. Diabetic nephropathy in Type I (Insulin- dependent) Diabetes: An epidemiological study. Diabetologia 1983; 25: 496–501
Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 1984; 311: 89–93
Mauer SM, Chavers BM, Ste ff es MW. Should there be an expanded role for kidney biopsy in the management of patients with Type I diabetes? Am J Kidney Dis 1990; 16: 96–100

On the other side
NIDDM with renal involvement – 12-81% of renal lesions are non-diabetic renal diseases (NDRD)
Amoah E, et al. Clinical identification of nondiabetic renal disease in diabetic patients with Type I and Type II disease presenting with renal dysfunction. Am J Nephrol 1988; 8: 204–211
Richards NT, et al. Increased prevalence of renal biopsy findings other than diabetic glomerulopathy in type II diabetes mellitus. Nephrol Dial Transplant 1992; 7: 397–399
John GT, et al. Nondiabetic renal disease in noninsulin-dependent diabetes in a South Indian hospital. Nephron 1994; 67: 441–443
Suzuki Y, Ueno M, Hayashi H et al . A light microscopic study of glomerulosclerosis in Japanese patients with noninsulin dependent diabetes mellitus: the relationship between clinical and histological features. Clin Nephrol 1994; 42: 155–162
Kleinknecht D, Bennis D, Altman JJ. Increased prevalence of non-diabetic renal pathology in type II diabetes mellitus ( letter). Nephrol Dial Transplant 1992; 7: 1258–1259
Olsen S, Mogensen CE. How often is NIDDM complicated with non-diabetic renal disease? An analysis of renal biopsies and the literature. Diabetologia 1996; 39: 1638–1645
Prakash J et al. Non-diabetic renal disease in Type 2 diabetes mellitus. J Assoc Physicans India. 2001 April, 49:415-20.

Type II DM with renal disease:
Usually we don’t biopsy them
A retrospective analysis was performed on biopsy reports of patients who had undergone native renal biopsy
53.2% with a pathologic diagnosis of NDRD
27.5% with pure diabetic glomerulosclerosis
19.3% with concurrent NDRD and DGS
FSGS (21%), minimal change (15.3%), IgA nephropathy (15.6%%), membranous GN (13.3%)
Prevalence of nondiabetic renal disease in diabetic patients. Pham TT et al. Am J Nephrol. 2007;27(3):322-8

NDRD - renal lesions:
Membranous nephropathy , minimal change disease, IgA nephropathy , focal glomerulosclerosis, Henoch-Schönlein purpura, thin basement membrane disease, proliferative glomerulonephritis
Heterogeneous nature of renal lesions in type II diabetes. Gambara V; Mecca G; Remuzzi G; Bertani T J Am Soc Nephrol 1993 Feb;3(8):1458-66.
Prevalence and causes of albuminuria in non-insulin-dependent diabetic patients. Parving HH; Gall MA; Skott P; Jorgensen HE; Lokkegaard H; Jorgensen F; Nielsen B; Larsen S Kidney Int 1992 Apr;41(4):758-62.
Causes of albuminuria in patients with type 2 diabetes without diabetic retinopathy. Christensen PK; Larsen S; Horn T; Olsen S; Parving HH Kidney Int 2000 Oct;58(4):1719-31.
Nondiabetic renal disease in patients with diabetes mellitus. Kasinath BS; Mujais SK; Spargo BH; Katz AI Am J Med 1983 Oct;75(4):613-7.
Insulin deposits in membranous nephropathy associated with diabetes mellitus. Furuta T; Seino J; Saito T; Sato H; Agatsuma J; Ootaka T; Satoh T; Yoshinaga K Clin Nephrol 1992 Feb;37(2):65-9.
The occurrence of IgA-nephropathy in patients with diabetes mellitus may not be coincidental: a report of five cases. Gans RO; Ueda Y; Ito S; Kohli R; Min I; Shafi M; Brentjens JR Am J Kidney Dis 1992 Sep;20(3):255-60.
Henoch-Schonlein purpura in a patient with diabetic nephropathy: case report and a review of the literature. Padilla B; Weiss M; Kant KS Am J Kidney Dis 1992 Aug;20(2):191-4.
Thin glomerular basement membrane in diabetic patients with urinary abnormalities. Matsumae T; Fukusaki M; Sakata N; Takebayashi S; Naito S Clin Nephrol 1994 Oct;42(4):221-6.
Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus. Mak SK; Gwi E; Chan KW; Wong PN; Lo KY; Lee KF; Wong AK Nephrol Dial Transplant 1997 Dec;12(12):2588-91.
Identification of non-diabetic glomerular disease in renal biopsies from diabetics--a dilemma. Olsen S Nephrol Dial Transplant 1999 Aug;14(8):1846-9.
Different patterns of renal damage in type 2 diabetes mellitus: a multicentric study on 393 biopsies. Mazzucco G; Bertani T; Fortunato M; Bernardi M; Leutner M; Boldorini R; Monga G Am J Kidney Dis 2002 Apr;39(4):713-20.
ARF in 2 patients with long-standing type 2 diabetes mellitus. Hill PA; Barit D; Toussaint N Am J Kidney Dis 2005 Feb;45(2):429-34.
Prevalence of nondiabetic renal disease in diabetic patients. Pham TT; Sim JJ; Kujubu DA; Liu IL; Kumar VA Am J Nephrol. 2007;27(3):322-8. Epub 2007 May 9.

NDRD: other possible causes -
Drugs - ACE inhibitors/ARB
Infection
Contrast nephropathy
Poorly controlled hypertension

Clinical clues suggesting NDRD:
Onset of proteinuria < 5 years from the documented onset of diabetes
The acute onset of renal disease or acute rise in proteinuria
Presence of an active urine sediment containing red cells and cellular casts
In type 1 diabetes - the absence of diabetic retinopathy or neuropathy
Signs and/or symptoms of other systemic disease
Significant reduction in the glomerular filtration rate (>30 %) within 2 –3 months of the administration of ACE inhibitors or ARB

Retinopathy and nephropathy:
Patients with nephropathy and Type 1 DM - almost always have retinopathy and neuropathy
The converse not true
Less predictable in Type II DM
27 patients with DM and proteinuria – confirmed diabetic nephropathy by biopsy – 56% had diabetic retinopathy
Causes of albuminuria in patients with type 2 diabetes without diabetic retinopathy. Christensen PK; Larsen S; Horn T; Olsen S; Parving HH Kidney Int 2000 Oct;58(4):1719-31.

Retinopathy and nephropathy:
2007 K/DOQI Guidelines for diabetes and chronic kidney disease
chronic kidney disease should be attributed to diabetes in most patients with diabetes if microalbuminuria and diabetic retinopathy are both present
By comparison, other causes of CKD should be entertained if diabetic retinopathy is absent

Conclusion:
Diabetic nephropathy is the commonest cause of CKD and ESRD
Most likely diagnosis in Type I DM with long duration and retinopathy
Also a more likely diagnosis in Type II DM with retinopathy and microalbuminuria
Acute onset of renal impairment with no previous documentation of albuminuria – consider other renal causes
Think of medications including traditional drugs

The Other Side Of A Coin 1

by KW Wong on Sep 21, 2008

Accessibility

Categories

Upload Details

Usage Rights

1 Embed 1

Statistics

The Other Side Of A Coin 1 Presentation Transcript