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.

Outcome and complications in peritoneal dialysis patients: a five-year single center experience.

Peritoneal dialysis (PD) is one of the modes of renal replacement therapy being utilized for the management of end-stage renal failure in King Khalid University Hospital, King Saud University, Riyadh, for more than two decades. The aim of this study was to evaluate the complications related to PD as well as its outcome in patients on this mode of therapy during the period between January 2004 and December 2008. There were 72 patients included in the study, of whom 43 were females. The average age was 50.7 ± 30.1 years (14-88 years). Diabetes was the leading cause of end-stage renal disease (ESRD) seen in 40.2% of the study patients. Twenty-eight patients (38.9%) were on continuous ambulatory peritoneal dialysis (CAPD) and 44 (61.1%) were on automated PD (nocturnal intermittent peritoneal dialysis, NIPD or continuous cycler peritoneal dialysis, CCPD). The mean duration on PD of the study patients was 25.5 ± 16.58 months (1-60 months). The peritonitis rate was one episode per 24.51 patient-months or one episode per 2.04 patient-years. The incidence of peritonitis per person-year was calculated as 0.42. The leading causative agent for peritonitis was Staphylococcus (32%). Exit-site infection (ESI) rate was one episode per 56.21 patient-months. The incidence of ESI was 0.214 per person-years. The most common infective organism for ESI was Pseudomonas aeru-ginosa (58.8%). At the end of 5 years, 35 patients were continuing on PD, 13 patients were shifted to hemodialysis (HD), nine patients underwent renal transplantation, and six patients were transferred to other centers. Among the 13 patients who were shifted to HD, four patients had refractory peritonitis, four others had catheter malfunction, three patients had inadequate clearance on PD and two patients had lack of compliance. A total of 11 patients died during the study period, giving an overall mortality rate of 15.27% for the five-year period. Our study suggests that there has been considerable improvement in overall outcome and mortality in patients on PD. Additionally, a marked reduction in the infectious and non-infectious complications was noted with the peritonitis and ESI rates in our center being comparable to other studies and international guidelines.

Peritoneal membrane characteristics in patients on peritoneal dialysis.

Peritoneal dialysis (PD) is a well-established modality for treatment of patients with end-stage renal disease, giving excellent patient and technique survival rates. In Saudi Arabia, data collected by the Saudi Center for Organ Transplantation showed that in 2008, patients on PD accounted for a mere 4.8% of total patients on renal replacement therapy, including hemodialysis and renal transplantation. This study was conducted to identify the characteristics of membrane permeability in the Saudi population and to assess the role of various factors affecting solute transport across the peritoneal membrane. We followed up a total of 52 patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) as well as Automated Peritoneal Dialysis (APD), being treated in the PD unit of the King Khalid University Hospital, Riyadh. There were 30 female and 22 male patients; 14 patients were using CAPD while 38 patients were on APD. The mean age of the patients was 50.5 years, with a range of 14-86 years. The average body mass index (BMI) was 27.1 kg/m² and the mean body surface area (BSA) of the study patients was 1.71 m². A standardized PET test was performed on all patients, 4-6 weeks after initiation of regular PD. The Kt/V and creatinine clearance measured 6-8 weeks after initiation of dialysis were 1.96 and 56.59 L/week, respectively. Residual renal function was assessed on the basis of daily urine output, using 24-hour urine collection. The mean serum urea con-centration was 16.91 mmol/L and mean serum creatinine was 702 µmol/L. According to the Peritoneal Equilibration Test (PET), 8% of the subjects belonged to the high trans-porter category, 44% patients belonged to the high-average transport group, 46% to the low-average category and 2% came in the low transporter category. Our study suggests that the patient characteristics and demographic para-meters seen in the Saudi population are comparable to those seen in other studies from the Middle East and worldwide, including data collected from Canada, New Zealand and Mexico.

Serum cystatin C: a surrogate marker for the characteristics of peritoneal membrane in dialysis patients.

To evaluate whether cystatin C levels can be a surrogate marker of creatinine clearance and reflect the characteristics of peritoneal membrane in dialysis patients, we performed peritoneal equilibration tests (PET) in 18 anuric adult chronic peritoneal dialysis (PD) patients with a mean age of 39.7 +/- 20 years. All the samples were analyzed for urea, creatinine, and cystatin C. Peritoneal transport, mass transfer, and peritoneal clearance of cystatin C were calculated. Correlation and regression analysis was done using cystatin C as a dependent variable and age, sex, height, weight, body surface area, and creatinine as independent variables. Cystatin C demonstrated a significant time dependent increase of dialysate concentration and decline in the serum concentrations during PET, and a strong correlation between serum creatinine and serum cystatin C concentrations(r: 0.62, p= 0.008). The trans-peritoneal clearance (mL/min/1.73 m 2 ) of cystatin C was related to its serum concentration and was similar to creatinine in its pattern but of smaller magnitude. Peritoneal mass transfer (mg/4 hr per 1.73 m 2 ) for cystatin C serum creatinine was 1.68 +/- 0.67 and 73.3 +/- 29.8, respectively. The dialysis/plasma D/P cystatin C concentration was > or = 0.1 at 4 hrs of PET denoted high peritoneal transport, while the values of < 0.1 denoted low transport type. We conclude that cystatin C follows the same pattern of peritoneal exchange as creatinine but the magnitude of transfer is many folds lower than creatinine. At present clinical utility of cystatin C in the evaluation of solute clearance is probably limited due to the minute amounts transferred across the membrane and the high renal clearance in the presence of residual renal function.

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.

Normal reference levels of serum cystatin C in Saudi adults.

This is the first report from Saudi Arabia studying the normal reference intervals in adult Saudi subjects and evaluating serum cystatin C as a prospective marker for the assessment of the glomerular filtration rate (GFR). Three hundred healthy adult Saudi subjects including 156 males (52%) and 144 females (48%), with a mean age of 31.21 +/- 9.82 years were prospectively studied to establish normal reference ranges for cystatin C. A total of 68.34% of the study patients were in the age-group of 21-40 years. The mean serum cystatin C in the 300 healthy subjects was 0.751 +/- 0.11 mg/L (0.50 - 1.09), increasing gradually with age: it was 0.738 +/- 0.11 mg/L (0.51 - 1.09) in the age-group 21 - 30 years and 0.807 +/- 0.12 (0.51 - 1.09) among subjects who were > 50 years of age. The mean serum cystatin C in females (0.778 +/- 0.118 mg/L) was significantly hig-her than in males (0.726 +/- 0.095 mg/L) (p < 0.0001). The serum cystatin C level was within the defined reference range of 0.53 - 0.95 mg/L in 95% of the subjects with a mean value of 0.74 +/- 0.097 mg/L, and was falling within the 95% confidence interval of 0.73865 - 0.7637 mg/L, and with 98.84% area under the curve (AUC). All the other renal function markers (urea, serum creatinine, calculated GFR, BMI) among the studied subjects were within the normal reference ranges for adult Saudi population. The serum cystatin C level had a significant correlation with the body mass index (BMI) (r = 0.155; p = 0.007) and a correlation with serum creatinine as well (r = 0.009; p = 0.873). It showed a negative correlation with calculated GFR as per Cockroft-Gault equation (r = - 0.101; p = 0.083).

Electrocardiography and serum potassium before and after hemodialysis sessions.

This study was undertaken to assess potassium level and electrocardiographic (ECG) changes post hemodialysis and whether fall in potassium level during dialysis may potentiate cardiac arrythemia. We studied 21 chronic hemodialysis (HD) patients who had their serum electrolytes measured before and immediately after dialysis session, and ECG performed at the same time. The patients included 14 females and 7 males with a mean age of 53.1+/-15.6 years and range from 26 to 81 years; 9 (43%) patients were diabetics. All the patients had been on dialysis for a minimum of 6 months each Pre-HD serum potassium levels had no correlation with any ECG parameters except a negative correlation with the T wave amplitude r=-0.5, p=0.021. ECG parameters significantly changed post-HD; the T wave amplitude decreased, and the R wave amplitude increased. A comparatively higher R wave significantly decreased the T to R wave ratio post dialysis. The QRS duration and QTc interval also increased significantly. The patients with post-HD serum potassium of < or = 3.5 -in comparison to those with levels > 3.5 mmol/L -had a higher R wave amplitude and a significantly less T to R wave ratio (11.8+/-9.7 vs 6.4+/-5.1, p=0.045 and 0.4+/-0.38 vs 1.0+/-0.97, p=0.049, respectively. In patients with serum potassium decrement of > 2.0 mmol/L, the T to R wave ratio decreased significantly, 0.32+/-0.21 vs 0.85 +/-0.26, p=0.023; The T wave amplitude decreased more than the rise in R wave. Multiple regression analysis did not reveal any relationship of pre or post HD ECG changes and serum potassium, serum calcium or net change in serum potassium post-HD. We conclude that post-HD serum potassium decrement results in a decrease in T to R wave ratio on ECG; this change may have an arrhythmogenic potential.

Complications of CAPD: A Single Center Experience.

To evaluate the complications of CAPD and their contributing factors in order to improve the patients' survival and reduce morbidity and mortality, we studied records of 65 CAPD patients treated at our hospital from October 1996 to January 2002. There were 32 (49%) males and the mean age of the patients was 48 +/- 16 years. All the patients were on the twin bag CAPD system. The mean duration of follow-up on CAPD was 29 +/- 20 months. There were 75 episodes of complications occurring in the patients with a rate of 0.41 episodes/patient years. Peritonitis was the most frequent and serious complication accounting for 55 episodes with a rate of 0.35 episodes/patient years. Only 51% of the episodes showed positive culture; the organisms included Staphylococcus epidermidis (18.2%), Staphylococcus aureus (3.6%), Pseudomonas (16.4%), E. coli (1.8%), Azadobacter (5.45%) and Serratia (3.6%). All the episodes of infection, except one, responded to treatment but 10 patients had recurrent infection; one patient was cured only after removal of the catheter. There were 12 exit site infection episodes and five catheters were removed due to mechanical and infectious reasons. Three patients were switched to hemodialysis (HD), nine patients were transplanted and 11 patients expired; none died due to peritonitis. We conclude that the mortality rate of the complications on CAPD has declined in the present study compared to our previous report early in the 1990s due mostly to the adoption of the twin bag CAPD system.

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.

Transverse myelitis in a patient with severe lupus nephritis: a case report.

We report here a case of severe lupus nephritis, Raynaud's phenomenon, digital gangrene and optic neuritis who, developed acute transverse myelitis (ATM). SLE can present virtually with any complication in the central nervous system (CNS) and ATM is a rare but serious manifestation. It is noteworthy that ATM developed in this patient while she was on intravenous cyclophosphamide (IVC) therapy having already finished six doses of monthly infusions of 10 mg/kg body weight. The patient responded well to methyl-prednisolone pulse therapy, IVC and plasmapheresis. She recovered fully and is doing well after nine months of follow-up.

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.