Comparison of high and low dose of cyclophosphamide in lupus nephritis patients: a long-term randomized controlled trial.

To evaluate the outcome of low doses of cyclophosphamide (Cyclo) therapy in lupus nephritis (LN) patients, we studied 117 biopsy-proven, de novo LN WHO class IV patients double-blinded and randomized in December 1997 to receive Cyclo in different doses; Group I (n=73) received Cyclo 10 mg/kg monthly for six months then every two months for 12 months. Group II (n=44) received Cyclo 5 mg/kg monthly for six months then every two months for 36 months. The patients were followed-up till January 2007. Six months post-induction values for creatinine clearance were significantly higher in Group I (67.7 ± 28.6 mL/min) compared with Group II (55.1 ± 30.1 mL/min), P = 0.026. Serum C4 and ANA were not significantly different between the groups (P > 0.05). At the mean follow-up of 6.77 ± 3.3 years, the mean creatinine clearance was 44.74 ± 31.7 mL/min in Group I vs. 49.3 ± 38.8 in Group II. Urinary protein was 1.65 ± 1.8 g/dL in Group I vs. 1.02 ± 1.01 in Group II (P = 0.03). The survival curve showed that kidney survival overtime was comparable in both groups (P = 0.2). Complete remission was observed in 25 (34.2%) patients in Group I vs. 11 (25%) in Group II (P = 0.288), while partial remission was similar in both groups; 43 (58.9%) patients in Group I vs. 26 (59%) patients in Group II. End-stage renal disease was observed in 10 (13.7%) patients in Group I vs. 9 (20.4%) patients in Group II (P = 0.359). Side-effects were more frequent in Group I patients than in Group II patients; gonadal toxicity and malignancy were lower in Group II patients (P = 0.0000). Moreover, different infections occurred in 23 (31.3%) patients vs. six (13.6%), digital infarcts occurred in 1.35% vs. 0%, diabetes in 4.1% vs. 2.27%, and vasculitis in 4.1% vs. 2.27% in Group I vs. Group II, respectively. Sustained amenorrhea without pregnancy was observed in both groups; however, significantly more in Group I patients, P ≤ 0.05. We conclude that low-dose Cyclo therapy is sufficiently effective for WHO class IV LN patients with lower side-effects compared with standard dose.

Microvascular and macrovascular complications in diabetic nephropathy patients referred to nephrology clinic.

To evaluate the diabetic complications and fate of diabetic nephropathy in Saudi population, we studied 184 diabetic nephropathy (DN) patients who were referred to nephrology clinic of King Khalid University Hospital, Riyadh, Saudi Arabia from January 2003-June 2006. The patients had mean age of 61.9 +/- 13.1 years, included 128 (69.6%) males, and were followed up for a mean period of 10.2 +/- 1.5 years. The mean duration of diabetes mellitus (DM) was 19.5 +/- 5.8 years, and duration of nephropathy was 7.7 +/- 3.3 years. Family history of DN was documented in 52 (28.2%) patients. At initial visit, the mean systolic blood pressure was 164 +/- 14.5 mmHg, the mean diastolic blood pressure was 97.9 +/- 10.4 mmHg. Thirty-seven (20%) patients had normal BMI, 88 (48%) were overweight, while 55 (30%) were obese. Mean creatinine clearance was 51.7 +/- 26.3 mL/min, 24 hrs urinary proteins 1.99 +/- 2.48 gm/day, HbA1C 9.2 +/- 1.8 %, triglyceride 2.1 +/- 1.3 mmol/L, and cholesterol 5.17 +/- 1.54 mmol/L. Diabetic complications included angiography proven coronary artery disease in 106 (57.6 %) patients, stroke in 21 (11.4%), myocardial infarction (MI) in 27(14.6%), angina in 87 (47.2 %), retinopathy in 82 (44.5%), Blindness in 3 (1.6%), peripheral vascular disease in 121 (65.7%), Neuropathy in 123 (66.8%), hypertension in178 (96.7%), diabetic foot in 25 (13.5%), Amputation in 10 (5.4%), and end-stage renal disease in 70 (38%). Total of 13 (7.05%) patients died in the hospital. Thirty-seven percent of patients developed > 6 concomitant complications. 28% developed 5, 17% developed 4, and the rest developed < 3. DN was relatively refractory to therapy and progressive; 123 (66.8%) patients doubled their serum creatinine in 3.59 +/- 2.88 years, 32 (17.3%) maintained stable renal function, 136 (73.6 %) deteriorated, and 12 (6.52%) improved. we conclude that the prevalence of diabetic complications is high among Saudi patients, and many had multiple complications. Baseline creatinine clearance and proteinuria, high systolic blood pressure, advanced age, and longer duration of diabetes were the most significant risk factors for developing complications.

Spectrum and outcome of primary glomerulonephritis.

Glomerulonephritis (GN) is a major cause of chronic renal failure (CRF). To evaluate the trends and outcome with modern improved treatment strategies, we retrospectively reviewed the clinical records of 120 patients with biopsy proven primary GN at our center from January 1990 to June 2001. All the biopsy specimens were subjected to light, electron and immunofluorescent microscopy. The recorded clinical parameters included the presenting symptoms, blood pressure readings, complete blood count, urinalysis, 24-hr urinary protein excretion, creatinine clearance besides rendered therapy and the outcome. Focal segmental glomerulosclerosis was the most common GN and accounted for 56 (47.6%) cases. The frequency of other GN cases in our study included IgA GN in 21 (17.5%) patients, membranous GN in 20 (16.7%), minimal change disease (MCD) in 13 (10.8%), membranoproliferative GN in 4 (3.3%), post infection in 4 (3.3%) and rapidly progressive glomerulonephritis (RPGN) in 2 (1.7%). The type of nephropathy had great influence on outcome and response to therapy. The deterioration of patients with FSGS was the fastest of the glomerulopathies, and nine (16.1%) patients developed end-stage renal failure (ESRD). MCD and post infection GN had the best outcome. Corticosteroids alone along with supportive medication conferred good results in MCD, while combined therapies of mycophenolate mofetil (MMF) and/or cyclophosphamide with corticosteroids provided better outcomes in the rest of the GN. RPGN responded well to the cyclophosphamide and the patients did not develop ESRD. Hyperuricemia, high serum creatinine and hypertension predicted worse outcomes. The control of blood pressure and glucose, and treatment of hyperuricemia and hypoalbuminemia had salutary effect on the outcome. We conclude that due to the better delivered care the outcome of primary GN has improved over the years. However, FSGS is still the most frequently encountered primary GN and has the worst outcome. In the present study, combined therapies with corticosteroids and cytotoxic drugs and supportive therapy were associated with better outcome.

Single Center Experience with Pre-dialysis Patients.

The objective of this study was to evaluate the effect of the management of factors accelerating renal injury such as hypertension and diabetes on progression of chronic renal failure (CRF). For this end, the records of 112 CRF patients with serum creatinine (SCr) level of 150- 850 micromol/L were retrospectively studied at King Khaled University Hospital in Riyadh, Saudi Arabia. The leading causes of CRF in the study patients were diabetes in 52 (46.4%) patients, glomerulonephritis in 25 (22.4%) and hypertension in 17 (15.2%). Progressive elevation of SCr level was recorded at 92 micromol/L/year in 62 (55.4%) patients with initial SCr level of 150-300 micromol/L; they progressed to end stage renal disease (ESRD) in a mean duration of 4 (1/2) years. Forty-three (38.4%) patients with SCr level of 300-450 micromol/L had an increase of SCr at 136 micromol/L/year and progressed to ESRD in a mean period of four years. Seven (6.2%) patients who had initial SCr level of > 450 micromol/L had an increase of 136 micromol/L/year and progressed to ESRD in a mean duration of 2 (1/2) years. Sixty-two (55.4%) patients had initial blood pressure (BP) readings above the recommended level of 130/80 mm Hg. Antihypertensive management stabilized 47 (75.8%) of these patients using multiple drug regimens such as an angiotensin converting enzyme (ACE) inhibitor and diuretics (20.5%). Though this center did not use erythropoietin (EPO) in these patients, the control of the levels of hemoglobin and hematocrit was obtained by aggressive iron supplementation including intravenous administration. In conclusion, the present management of CRF patients, which attempts to comply with the international standards, still needs refining in order to reach better outcome.