Childhood primary glomerular diseases in the western region of Saudi Arabia

We report our institute experience on primary glomerular disease in children in the western region of Saudi Arabia over the last 18 years (1988 to 2006). A total of 169 cases were identified as primary glomerular diseases in children and adolescent with age range from first year of life till 18 years. Minimal change disease and focal segmental glomerulosclerosis were the com-monly encountered primary glomerular diseases (20.1%and 19.5% respectively), mesangioprolifera-tive glomerulonephritis IgM nephropathy (14.8%), IgA nephropathy (10.7%), postinfectious glome-rulonephritis (9.5%), membranous glomerulonephritis (7.1%), membranoproliferative glomerulone-phritis (5.9%) and mesangioproliferative glomerulonephritis with negative immunofluorescence (5.9%). The less frequently encountered primary glomerular diseases were congenital nephritic syn-drome Finnish type (2.4%), Alport syndrome (2.4%), dense deposit disease (1.2%), and mesangio-proliferative glomerulonephritis with IgG positive (0.6%). We concluded that minimal change di-sease and focal segmental glomerulosclerosis are the most common primary glomerular disorder en-countered in children in our series and with similar age distribution

Concomitant macro and microvascular complications in diabetic nephropathy

To determine the prevalence of concomitant microvascular and macrovascular complica-tions of diabetic nephropathy we retrospectively reviewed the medical records of all 1,952 type 2 dia-betic patients followed-up at Security Forces Hospital, Riyadh, Saudi Arabia from January 1989 to December 2004. There were 626 (32.1%) patients (294 (47%) were males) who developed diabetic nephropathy. Their mean age was 66.9 ± 11.4 years, mean duration of diabetes was 15.4 ± 7.5 years, mean age at the onset of nephropathy was 61.5 ± 12.4 years, and mean duration of nephropathy was 3.9 ± 3.8 years. Concomitant diabetic complications included cataract (38.2%), acute coronary syndrome (36.1%), peripheral neuropathy (24.9%), myocardial infarction (24.1%), background retinopathy (22.4%), stroke (17.6%), proliferative retinopathy (11.7%), foot infection (7.3%), limb amputation (3.7%) and blindness (3%). Hypertension was documented in 577 (92.2%) patients, dyslipidemia in 266 (42.5%) and mortality from all causes in 86 (13.7%). There were 148 (23.6%) patients with one complication, 81 (12.9%) with two, 83 (13.3%) with three, and 61 (9.7%) with four or more. Dete-rioration of glomerular filtration rate was observed in 464 (74%) patients and doubling of serum creatinine in 250 (39.9%), while 95 (15.2%) developed end-stage renal disease (ESRD) at the end of study and 79 (12.6%) required dialysis. Complications were significantly more prevalent among males with greater number reaching ESRD level than females (P< 0.05). Relative risks of developing com-plications were significant after the onset of nephropathy; ACS (1.41), MI (1.49), stroke (1.48), diabetic foot (1.6), amputation (1.58) and death (1.93). We conclude that complications of diabetes are aggre-ssive and progressive including high prevalence of diabetic nephropathy. Careful monitoring and proper institution of management protocols should be implemented to identify diabetic patients at high risk for complications and mitigate progression into ESRD

Hepatitis G virus (HGV) infection in Saudi dialysis patients and healthy controls

Background: Viral hepatitis is a global health problem with a high mortality rate. End stage renal disease (ESRD) patients have a high prevalence of Hepatitis B and C virus infection. Present study was done to identify the prevalence and course of a new isolate Hepatitis G virus (HGV) infection in Saudi dialysis patients. Methods: The pattern of viral hepatitis infection (HBV. HCV and HGV) was investigated in 109 Saudi patients with ESRD and 100 healthy Saudi blood donors. Donated blood was tested for markers of Hepatitis B, C and G viruses. Liver functions were measured and blood picture and liver biopsies were also performed at regular intervals. Results: Out of the 109 ESRD patients 68 (62.4%) were positive for at least one viral marker: 59 (54.1%) were positive for HCV, six (5.5%) were positive for HGV and three (2.8%) were positive for HBsAg. Four of the six HGV positive patients were also co-infected with HCV. Eight (8%) of the blood donors were positive for at least one viral marker. Elevated ALT levels (>4 times normal) were recorded in four out of the six HGV-positive patients including three co-infected with HCV. Conclusions: Our results are in agreement with similar studies from different countries and also raise the question about the causal relationship between HGV and liver disease among dialysis patients

Living Unrelated Renal Transplant: Outcome and Issues

Living unrelated transplantation (LURT) is emerging as a practical option in renal transplantation due to shortage of living related and cadaver donors. We report a six-years (December 1991 to December 1996) follow-up of 60 LURT patients. The majority of these patients (95%) were transplanted outside the Kingdom of Saudi Arabia; 37 in India, 14 in Egypt, five in the USA and one in Pakistan. Only three patients (emotionally related) were transplanted in Saudi Arabia. Before transplantation, 50 (83.4%) patients were on chronic hemodialysis, three (5%) on peritoneal dialysis and three (5%) were transplanted pre-emptively. Post-operatively, the majority of the study patients were on three drug immunosuppressive therapy. One and five year graft survival was 93.0% and 59.6%, while patient survival at one and three years was 93.7% and 81%, respectively. Surgical complications included lymphocele in 10% of the study patients, urinary leak in 8.3%, and bleeding from the vascular anastomosis in 6.6%. There were eight episodes of acute rejection in eight (13.3%) patients and all episodes were successfully treated; two patients required monoclonal anti-lymphocyte antibodies (OKT3). Eleven (18.3%) patients developed chronic rejection, which resulted in the loss of ten (90%) allografts. Infection was the commonest cause for hospital admission; urinary tract infection (UTI) being responsible for 40% of admissions. Three patients had Cytomegalovirus pneumonia, one had Pneumocystis Carinii pneumonia and one had candida pneumonia. Two (3%) patients developed Kaposi′s sarcoma. We conclude that LURT can help in overcoming the shortage of organs for transplant, however, commercial transplantion in developing countries is associated with high morbidity and mortality

Effect of Intravenous Cyclophosphamide Pulse Therapy on Renal Functions and Histopathology in Patients with Severe Lupus Nephritis

Despite the wide use of intravenous cyclophosphamide (IC) in lupus nephritis (LN), there are few published studies showing the effect of this treatment on renal histology. In this prospective study, we report the effect of IC on the evolution of histopathologic features in successive renal biopsies in patients with LN. Thirty patients with class IV or V LN were started on IC (10-15 mg/kg) administered once every month for six months followed by three monthly for another six doses making a total of two years of therapy. The clinical course of the disease, serum creatinine and 24 hours urinary protein and creatinine clearance were tested at entry and subsequently during each follow-up visit. Repeat renal biopsy was performed after completion of two years of therapy. The mean serum creatinine of the study patients was 166.3 <u> &#x002B;</u> 42 tmol/L at entry which decreased to 104 &#x002B; 46.4 tmol/L at two years (P &lt; 0.01). The mean 24 hours proteinuria decreased from 2.81 <u> &#x002B;</u> 2.4 g at entry to 1.39 <u> &#x002B;</u> 1.54 g at two years (P &lt; 0.003) and the mean creatinine clearance increased from 58 <u> &#x002B;</u> 31 ml/min at the start of treatment to 64 <u> &#x002B;</u> 32 ml/min at two years of therapy (P &lt; 0.05). Nine patients had serum creatinine of &gt; 200 tmol/L, of whom six progressed to variable degrees of chronic renal failure. Repeat renal biopsy was performed in 21 patients. The original biopsy of these patients showed class IV in 17 and class V in four patients. On repeat biopsy, five of class IV disease had progressed to advanced sclerosis, four to class V, and five remained unchanged. The remaining three patients with class IV LN changed to one each of class I, II and III. Of the four patients with class V, one progressed to advanced sclerosis, one changed to class III and two remained the same. There was a significant decrease (P &lt; 0.05) in the activity index although there was a significant increase in the chronicity index (P &lt; 0.001). Multivariat analysis for possible risk factors for progression to chronic renal failure showed initial high serum creatinine to be a powerful predictor of renal failure. In conclusion, IC pulse therapy is effective in improving or stabilizing renal function in patients with class IV or V LN. The only poor prognostic determinant observed was higher initial serum creatinine value

Diabetes complications in 1952 type 2 diabetes mellitus patients managed in a single institution

Background and Objectives: Because there is no recent update on the state of diabetes and its concomi--tant complications in Saudi Arabia , we undertook a study of the prevalence of health complications in patients with type 2 diabetes mellitus admitted to our institution. Methods: We conducted a retrospective review of medical records of adult Saudi patients with type 2 diabetes who were seen in clinics or admitted to the Security Forces Hospital , Riyadh , Saudi Arabia , between January 1989 and January 2004. Results: Of 1952 patients , 943 (48.3&#x0025;) were males. For the whole study population the mean age at enrollment was 58.4&#x00B1;14.2 years , the mean age at onset of diabetes was 48.1&#x00B1;12.8 years , the mean duration of diabetes was 10.4&#x00B1;7.5 years , and the mean duration of follow-up was 7.9&#x00B1;4.6 years. Nephropathy was the most prevalent complication , occurring in 626 patients (32.1&#x0025;). Acute coronary syndrome occurred in 451 (23 .1 &#x0025;), cataracts in 447 (22.9&#x0025;) , retinopathy in 326 (16.7&#x0025;) , and myocardial infarction in 279 (14.3&#x0025;) , Doubling of serum creatinine was seen in 250 (12.8&#x0025;) and 79 (4.0&#x0025;) went into dialysis. Hypertension was present in 1524 (78.1&#x0025;) and dyslipidemia in 764 (39.1&#x0025;). Overall mortality was 8.2&#x0025;. Multiple complications were frequent. Males had higher prevalence of complications than females (P&#60; .05). Mortality was significantly higher in males 92 (9.8&#x0025;) than females 69 (6.8&#x0025;) (P=.024). The prevalence of complications significantly increased with dura--tion of diabetes and age (P&#60; .05). Conclusion: Among Saudis, the prevalence of concomitant diabetic complications is high, with cardiovas--cular and renal complications the most frequent. Many patients had multiple complications. Early and frequent screenings in the patients with type 2 diabetes are desirable to identify patients at high risk for concomitant complications and to prevent disabilities

Multitargeted Virtual Screening and Molecular Simulation of Natural Product-like Compounds against GSK3β, NMDA-Receptor, and BACE-1 for the Management of Alzheimer’s Disease

The complexity of Alzheimer’s disease (AD) and several side effects of currently available medication inclined us to search for a novel natural cure by targeting multiple key regulatory proteins. We initially virtually screened the natural product-like compounds against GSK3β, NMDA receptor, and BACE-1 and thereafter validated the best hit through molecular dynamics simulation (MDS). The results demonstrated that out of 2029 compounds, only 51 compounds exhibited better binding interactions than native ligands, with all three protein targets (NMDA, GSK3β, and BACE) considered multitarget inhibitors. Among them, F1094-0201 is the most potent inhibitor against multiple targets with binding energy −11.7, −10.6, and −12 kcal/mol, respectively. ADME-T analysis results showed that F1094-0201 was found to be suitable for CNS drug-likeness in addition to their other drug-likeness properties. The MDS results of RMSD, RMSF, Rg, SASA, SSE and residue interactions indicated the formation of a strong and stable association in the complex of ligands (F1094-0201) and proteins. These findings confirm the F1094-0201’s ability to remain inside target proteins’ binding pockets while forming a stable complex of protein-ligand. The free energies (MM/GBSA) of BACE-F1094-0201, GSK3β-F1094-0201, and NMDA-F1094-0201 complex formation were −73.78 ± 4.31 kcal mol−1, −72.77 ± 3.43 kcal mol−1, and −52.51 ± 2.85 kcal mol−1, respectively. Amongst the target proteins, F1094-0201 have a more stable association with BACE, followed by NMDA and GSK3β. These attributes of F1094-0201 indicate it as a possible option for the management of pathophysiological pathways associated with AD