Mohammed Alghonaim

Strategy for second kidney biopsy in patients with lupus nephritis

BACKGROUND Standard clinical and laboratory parameters have limited predictive values for discriminating between active lupus nephritis and chronic disease. The objective of this study was to examine the predictive utility of a second kidney biopsy in patients with lupus nephritis. METHODS Patients with lupus nephritis were advised to have second kidney biopsies at the end of the maintenance phase of their therapies. Baseline and second renal biopsies were re-classified by pathologists blinded to the clinical data. The relationships between remission status and histological parameters were examined. RESULTS Included in this study were 77 patients followed up for a median duration of 8.7 years (interquartile range, 5.3-10.1 years). Their renal survival rates were 93% for those in complete remission (CR), 69% for partial remission (PR) and 41% for no remission (NR). One-third of the patients with PR and 14% of patients with NR had no histological evidence of active disease on second biopsy. At the second biopsy, but not at the baseline biopsy, activity index was predictive of survival. The 10-year renal survival rate was 100% for those with an activity index of 0, 80% for those with an activity index of 1 or 2 on the second biopsy and 44% for those with an index of >2, regardless of remission status. CONCLUSION Second kidney biopsy at the end of maintenance phase of therapy is an important diagnostic and prognostic tool that could guide physicians to safer practices with better outcomes.

Impact of early chronic kidney disease on maternal and fetal outcomes of pregnancy

Background. Elevated serum creatinine is associated with higher maternal and fetal risks; however, the influence of milder degree of renal impairment diagnosed on basis on estimated glomerular filtration rate (eGFR) is less well defined. This study assesses the impact of early chronic kidney disease (CKD) utilizing eGFR in predicting adverse outcomes in women with CKD. Methods. We analyzed outcomes of 98 pregnant women with CKD. Women with CKD stage 1 were used as control. Results. Women with eGFR of 60–89 ml/min were at an increased risk for deterioration of renal function, preeclampsia, and cesarean section. The odd ratios for composite maternal complication of worsening of renal function or preeclampsia were 6.75 (95% confidence interval (CI), 1.84–24.80) in women with eGFR of 60–89. Similarly, women with an eGFR of 60–89 had a significantly increased risk for intrauterine growth restriction (38.5%), preterm birth (31.2%), and intrauterine fetal death (15.8%). The odds for composite fetal adverse outcomes were 2.91 (95% CI, 1.19–7.09) in women with eGFR of 60–89. Conclusions. Early CKD increases the risk of adverse outcomes in pregnancy. Estimated GFR ranging between 60–89 ml/min/1.73 m2 is associated with significant maternal and fetal complications. The risk of adverse outcomes in pregnant women with early CKD can be more accurately stratified by using estimated GFR than the serum creatinine alone.

Gender Disparities in the Awareness and Control of Hypertension

Hypertension is an important risk factor for the commonest cause of death among men, namely, cardiovascular diseases. The purpose of this study was to provide data concerning gender difference in the awareness, treatment, and control of hypertension in adults. We conducted a cross-sectional study in Riyadh, the capital city of Saudi Arabia. Subjects were asked if they had been told by a physician that they had hypertension or were on blood pressure (BP) medication. Blood pressure was measured using standardized Joint National Committee (JNC) protocol. The study sample consisted of 814 adults who were at least 18 years old. Of the estimated 27.6% people with hypertension, 38.6% were unaware of their hypertension, 29.8% were aware of their condition but were not being treated, and among those who had been treated 40.8% remained uncontrolled. Independent predictors of a lack of awareness of hypertension were an age of at least 45 years, male gender, and BMI greater than 30. The extent of awareness and control of hypertension did not differ significantly by monthly income, educational level, physical activities, or smoking status. Awareness and control of hypertension is low in men, making them public health priorities. Achieving more stringent BP control will require increased attention by physicians and public education to improve the awareness and control of hypertension.

Assessment of the diagnostic value of different biomarkers in relation to various stages of diabetic nephropathy in type 2 diabetic patients

Albuminuria is widely used to indicate early phases of diabetic nephropathy although it is limited by the fact that structural damage might precede albumin excretion. This necessitates identifying better biomarkers that diagnose or predict diabetic nephropathy. This is a cross-sectional hospital based study recruiting type 2 diabetic patients cohort aged 35–75 years with diabetes duration of ≥10 years. Out of total eligible 467 patients, 200 patients were with normal albumin excretion, 184 patients with microalbuminuria and 83 patients with macroalbuminuria. All the patients were tested for the 22 selected biomarkers including serum, plasma and urinary markers. Sensitivity, specificity, and area under the curve (AUC) were calculated as measures of diagnostic accuracy. Out of the tested biomarkers, urinary transferrin, urinary Retinol binding protein (RBP) and serum osteopontin had the best diagnostic value for diabetic nephropathy presence based on the AUC value. The rest of the biomarkers had comparatively less or even no discriminative power. The urinary transferrin and RBP and serum osteopontin, had the best diagnostic value in type 2 diabetic patients at different stages of diabetic nephropathy. Further longitudinal prospective studies are needed to evaluate the predictive power of those markers for detecting diabetic nephropathy before any structural damage occurs.

Pulmonary hypertension in end-stage renal disease and post renal transplantation patients.

BACKGROUND Information regarding lung function parameters and functional capacity in renal failure and post renal transplantation patients with pulmonary hypertension (PH) is limited. The purpose of this study was to examine the clinical characteristics of patients with PH who were receiving hemodialysis (HD) or peritoneal dialysis (PD) or who had undergone renal transplantation. METHODS A prospective study was performed on 116 patients (HD =55, PD =17, and post renal transplantation =44) who underwent Doppler echocardiography. PH was defined as systolic pulmonary artery pressure (SPAP) ≥40 mmHg. Demographic information, clinical characteristics, pulmonary function tests (PFTs) and the six-minute walk test (6MWT) were collected and compared between the patients with and without PH. RESULTS Twelve (21.8%) patients receiving HD, four (23.5%) patients receiving PD, and eight (18.2%) post renal transplantation patients had PH. In the HD group, the physiological indicators (including pulmonary function test parameters, the final Borg score, and walking distance during the 6MWT) were all significantly lower in the patients with PH compared with those without PH (all P<0.0001). However, in the PD and post renal transplantation groups, no significant differences were noted in the demographic characteristics or in the physiological parameters when the PH patients were compared with those without PH (all P>0.05). CONCLUSIONS Among HD patients, marked aberrations in PFT results or walking distance may identify a subset of patients suffering from PH.

Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats

Methoxy poly(ethylene oxide)-block-poly(ɛ-caprolactone) (PEO-b-PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Mineral bone disorder and its management among hemodialysis patients in the Gulf Cooperation Council: Initial findings from the dialysis outcomes and practice patterns study (2012-2015)

The prospective cohort Dialysis Outcomes and Practice Patterns Study (DOPPS) initiated data collection in national samples of hemodialysis (HD) units (total of 41 study sites) in all six Gulf Cooperation Council (GCC) countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates) in late 2012. Here, we report initial results regarding mineral bone disorders (MBDs) and its management in the GCC countries. Forty-one randomly selected HD facilities, treating >23 HD patients each, were sampled and represent care for >95% of GCC HD patients. Descriptive results for the GCC countries based on a random sample of 20-30 HD patients in each study facility. Initial results for the GCC are from 931 HD patients treated at 41 dialysis units (ranging from 1 unit in Bahrain to 21 in Saudi Arabia). Results are presented as weighted estimates, accounting for the sampling fraction in each unit. Baseline descriptive statistics (e.g., mean, median, or percentage), weighted by facility sampling fraction were calculated for the study sample. For analyses examining the percent of facility patients having (a) serum phosphorus >6.0 mg/dL or (b) parathyroid hormone (PTH) >600 pg/mL, analyses were restricted to facilities having at least 10 HD patients with a reported serum phosphorus or PTH measurement, respectively. Logistic regression analyses of the indicated binary outcomes were based on the use of generalized estimating equations and were adjusted for GCC country, patient age category (<45 years, 45-65 years, and >65 years old), sex, and whether the patient was diagnosed with diabetes mellitus. Logistic models accounted for clustering of patients within facilities, assuming an exchangeable working correlation matrix. Mean age of HD patients in the GCC countries was 53 years vs. 61-64 years in the three other DOPPS regions. MBD markers showed slightly lower mean serum Calcium in the GCC countries, similar mean serum phosphorus, and intermediate median PTH levels compared with the three other DOPPS regions. Among GCC countries, the country mean value of MBD markers ranged from 8.6-9.0 mg/dL for serum calcium, 4.4-5.4 mg/dL for serum phosphorus, whereas median PTH ranged from 163-389 pg/mL. Similar to other DOPPS regions, PTH was higher among patients who were younger or without diabetes, and serum phosphorus was lower with older age (P <0.001 for each). History of parathyroidectomy was lower in the GCC countries versus other regions but did not differ when adjusted for age and dialysis vintage. Among treatments used for managing MBD, the GCC countries showed one of the highest uses of cinacalcet (24%) and phosphorus binder use (81%), whereas intravenous Vitamin D use (24%) was slightly higher than that in EURANZ. A much larger fraction of HD patients in the GCC countries had a dialysate calcium bath ≥3.5 mEq/L (43%) versus 0-4% in the three other DOPPS regions. Although many aspects of MBD management and MBD marker achievement are similar in the GCC countries to that seen in other DOPPS study regions, large variability was seen across countries and facilities in the GCC. Mean serum calcium was lower in the GCC despite the much greater use of dialysate Ca of ~3.5 mEq/L which may be due to the relatively low use of vitamin D and higher cinacalcet use, meriting further study. Future work will focus on GCC facility HD practices and patient characteristics most strongly related to the achievement of MBD target levels and associated outcomes.

Prevalence of vitamin D deficiency in peritoneal dialysis patients.

Peritoneal dialysis (PD) patients have a high risk of developing vitamin D deficiency as 25(OH) vitamin D, the precursor of active vitamin D, is lost during dialysis. This cross-sectional study was conducted to investigate the prevalence of vitamin D deficiency among adult Saudi patients on regular PD The data was collected in the summer of 2010 from patients who were on PD for more than six months at the King Khalid University Hospital, Riyadh. We recorded the demographic and clinical parameters for all patients. Blood samples were taken for serum vitamin D level (25 OH), serum parathyroid hormone (PTH) levels and other necessary biochemical parameters. There were 27 patients (11 males and 16 females) with a mean age of 46 (15-78 ± 21) years. Five patients were on continuous ambulatory PD and 22 patients were using automated PD. The average time on PD was 27.5 (6-84 ± 18.5) months. The mean serum vitamin D 25 (OH) level was 16.1 (4.9-41.5 ± 8.23) nmol/L. Sixteen (59.2%) of the patients had levels below 15 nmol/L, while another eight patients (29.6%) had vitamin D levels between 15 and 25 nmol/L, indicating a marked deficiency. The mean serum calcium was 2.2 (1.7-2.6 ± 0.2) mmol/L and the mean serum phosphorous was 1.48 (0.64-2.22 ± 0.37) mmol/L. Fifteen patients (55.5%) had significant hyperparathyroidism (serum PTH levels above 30 pmol/L). Majority of the PD patients in our center had vitamin D deficiency. The possible reasons include chronic renal failure, dietary restrictions, loss of vitamin D and decreased exposure to sunlight.

Neutrophil chemokines levels in different stages of nephrotic syndrome

Nephrotic syndrome (NS) is a disease of glomerular filtration barrier failure presenting with variable degrees of proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Inflammation may contribute to the pathogenesis of NS. The aim of this study was to monitor the serum levels of three cytokines [i.e., granulocyte chemotactic protein-2 (GCP-2), growth-related oncogene-α (GRO-α), and interleukin-8 (IL-8)] in different stages of NS and to find out whether changes in the levels of these cytokines could be related to the severity of NS. This study included 125 patients who were divided into 40 patients with nephrotic range proteinuria (NRP), 45 patients with NS, and 40 patients who were in remission. This study also included 80 healthy participants as a control group. Enzyme-linked immunosorbent assay was used for the determination of the plasma levels of GRO-α, GCP-2, and IL-8. GCP-2 plasma levels were significantly higher in the NS and NRP groups when compared to the control group, whereas the GRO-α and IL-8 levels were significantly higher in all patient groups in comparison with the control group. All these chemokine levels were significantly decreased in remission as compared with the participants in the NS group (P <0.0001). There was a significant correlation between the cytokine levels and proteinuria and serum albumin in the NS group (P <0.0001). However, in the follow-up group, GCP-2 levels were significantly lower during remission as compared to those with active NS (P <0.0001). Our findings suggest that the pro-inflammatory cytokines GCP-2, GRO-α, and IL-8 could play a role in the pathogenesis of NS, particularly glomerular permeability.

The Impact of Diabetes on Acute Post-Infectious Glomerulonephritis in Rats: An Experimental Study with Literature Review

Background: The concurrence of diabetes and nephritogenic infections may have a tremendous impact on the kidney. The approach to the two concurrent diseases is based on histological, immunofluorescence findings and most importantly on ultrastructural features. In this experiment our aim was to compare the pattern of injury seen in the kidney in animals with induced post-infectious glomerulonephritis with and without associated diabetes. Methods: We divided 48 Wistar species rats into four groups comprising twelve rats each. Group I is the normal control, group II includes the rats with induced diabetes, group III are the rats with acute post-infectious glomerulonephritis (APIG), while group IV includes the rats with induced diabetes and APIG. Streptozocin was used to induce diabetes in groups II and IV while neutral phosphatase toxin (NPTase) of Staphylococcus strain was used in groups III and IV. Groups III and IV were sacrificed three and ten days after infection. Routine, immunofluorescence and ultrastructural stains and studies were performed on the kidneys of all rats. Serum urea and creatinine and urinary protein were estimated in all groups. Results: Out of the forty-eight rats initially included in the study, only twenty-four survived the experiment: three in Group I, five in Group II, five in Group III and eleven in Group IV. The most relevant and distinguishing findings in cases of APIG with associated diabetes are the earlier and more prominent infiltration by polymorphonuclear cells, the stronger positivity for IgG and the earlier and more extensive presence of dense deposits which were confirmed by the electron microscopy study. Conclusions: This experiment ascertains the adverse effects of diabetes in cases of acute post-infectious glomerulonephritis, in terms of onset and severity of the disease. The necessity of a better control of the glucose level may not only decrease the incidence of acute post-infectious glomerulonephritis but may also contribute to the development of a milder form of the disease.