Chronic Kidney Disease Management in the Middle East and Africa: Concerns, Challenges, and Novel Approaches.

The burden of chronic kidney disease (CKD) and other comorbidities, such as hypertension and diabetes, which increase the risk of developing CKD, is on the rise in the Middle East and Africa. The Middle East and Africa CKD (MEA-CKD) steering committee, comprising eminent healthcare specialists from the Middle East and Africa, was formed to identify and propose steps to address the gaps in the management of CKD in these regions. The current article lists the MEA-CKD steering committee meeting outcomes and evaluates the available evidence supporting the role of novel therapeutic options for patients with CKD. The need of the hour is to address the gaps in awareness and screening, early diagnosis, along with referral and management of patients at risk. Measures to bring about appropriate changes in healthcare policies to ensure access to all benefit-proven protective therapies, including novel ones, at community levels are also vital for reducing the overall burden of CKD on the healthcare system as well as governing bodies, especially in developing countries of the Middle East and Africa.

Endotoxins and inflammation in hemodialysis patients.

Long-term endotoxin challenge may promote frequent complications in dialysis patients, namely malnutrition, chronic inflammation, and atherosclerosis, which are recognized as the so-called MIA syndrome. Circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) levels may be used to determine the stage of atherosclerosis. This study aimed to assess endotoxin level in hemodialysis (HD) patients and its role in inducing inflammation. The study was conducted on 50 HD patients, chosen from four dialysis centers in Alexandria. Serum blood samples were collected for the determination of albumin and C-reactive protein (CRP), and whole blood samples were used for the measurement of hemoglobin level. A heparinized whole blood sample was taken postdialysis for endotoxin assay by limulus amebocyte lysate test, and in addition to sVCAM-1 was estimated using enzyme-linked immunosorbent assay. The mean endotoxin level was 76.30 pg/mL;80% exhibited values higher than 60 pg/mL. Half the studied patients had CRP values that exceeded the upper limit of the laboratory reference range (<6.0 mg/L). A statistically significant correlation was found between endotoxin and CRP levels (r = 0.47, P = 0.001). The mean pre-HD level of VCAM was 1851.00 ng/mL, while the mean post-HD level was 2829.00 ng/mL with statistically significant correlation (r = 0.354, P = 0.012) and it also correlated significantly with endotoxin as well as CRP levels. Endotoxemia may play an important role in the aggravation of endothelial dysfunction in HD patients as indicated by the post-HD rise in sVCAM-1.

Bacteriological monitoring of dialysis fluid in 2 hemodialysis units in Alexandria, Egypt.

OBJECTIVE: To assess the bacteriological quality of dialysis fluid in 2 hemodialysis units in Alexandria, Egypt. METHODS: A total of 321 samples of hemodialysis fluids, 213 from unit A (a governmental unit), 108 from unit B (a private unit), both under the supervision of ministry of health, were collected from the water treatment system (WTS), treated water, concentrates, and final dialysate from the beginning of March to the end of August 2005. Samples were analyzed for enumeration of the total viable heterotrophic bacteria using the standard pour plate method, and for the determination of the total coliforms (TC) using the presence/absence method. Fifty samples were also examined for endotoxin detection by the Limulus Amoebocyte Lysate assay (LAL), employing the gel clot method. RESULTS: Percentages of acceptable samples of WTS were 67% from unit A and 66.7% from unit B, while the dialysate samples showed higher acceptability at unit B (86.1%) than unit A (51.7%). Eleven samples were detected as having TC. The LAL assay showed a range of 57-100% of samples exceeded 0.25 EU/ml. Analysis of these results and comparing them to other variables is further discussed. CONCLUSION: The results demonstrate that hemodialysis centers need monitoring and preventive maintenance in order to ensure renal replacement therapy of good quality.

Tissue transglutaminase and the progression of human renal scarring.

Experimental renal scarring indicates that tissue transglutaminase (tTg) may be associated with the accumulation of extracellular matrix (ECM), both indirectly via TGF-beta1 activation and directly by the formation of epsilon(gamma-glutamyl) lysine dipeptide bonds within the ECM. The latter potentially accelerates deposition and confers the ECM with resistance to proteolytic digestion. Studied were 136 human renal biopsy samples from a range of chronic renal diseases (CRD) to determine changes in tTg and epsilon(gamma-glutamyl) lysine crosslinking. Immunofluorescence for insoluble tTg showed a 14-fold increase in the kidneys of CRD patients (5.3 +/- 0.5 versus 76 +/- 54 mV/cm(2)), which was shown to be active by a similar 11-fold increase in the epsilon(gamma-glutamyl) lysine crosslink (1.8 +/- 0.2 versus 19.3 +/- 14.2 mV/cm(2)). Correlations were obtained with renal function for tTg and crosslink. In situ hybridization for tTg mRNA showed that tubular epithelial cells were the major source of tTg; however, both mesangial and interstitial cells also contributed to elevated levels in CRD. This mRNA pattern was consistent with immunohistochemistry for soluble tTg. Changes in renal tTg and its product, the epsilon(gamma-glutamyl) lysine crosslink, occur in progressive renal scarring in humans independently of the original etiology and in a similar manner to experimental models. tTg may therefore play a role in the pathogenesis of renal scarring and fibrosis in patients with CRD and can therefore be considered a potential therapeutic target.

Cytoskeletal protein expression and regenerative markers in schistosomal nephropathy.

BACKGROUND: Progression of renal diseases is related to the abnormal regulation of cellular and extracellular matrix turnover. Other factors in addition to schistosomal antigens may be relevant to the progression of schistosomal nephropathy (SN). The validity of markers of fibroblastic differentiation, alpha smooth muscle actin (alphaSMA), and vimentin, as well as the regenerative activity (PCNA/apoptosis index) in determination of progression of SN in comparison to other forms of non-schistosomal nephropathy (non-SN) is investigated. METHODS: Three groups were included; group I pure SN (n=16), group II a diverse group of non-schistosomal patients with comparable pathologic changes on renal biopsy (n=40) and a control group (n=5). Immunohistochemical staining of myofibroblasts (alphaSMA and vimentin) and proliferating cells (PCNA) and histomorphometric analysis was done. In situ end labelling (ISEL) of DNA was used to evaluate apoptosis. RESULTS: No differences in the patterns of distribution of positivity of the different studied markers were observed between the different nephropathy groups. Both alphaSMA and vimentin were detected in glomerular mesangial, tubular epithelial, interstitial inflammatory fibroblast-like cells and occasionally endothelial cells. PCNA and apoptotic cells were detected in tubular epithelial and interstitial cells with paucity of positive cells in the glomerulus. Significant positive correlations were detected in group I between glomerular sclerosis and interstitial markers including interstitial alphaSMA (r=0.609, P=0.001), interstitial vimentin (r=0.812, P=0.00) and interstitial apoptosis (r=0.733, P=0.001). On the other hand, glomerulosclerosis in group II showed significant positive correlations with predominantly the glomerular markers; glomerular alphaSMA (r=0.475, P=0.002), glomerular apoptosis (r=0.684, P=0.00) and glomerular PCNA (r=0.691, P=0.00). Interstitial fibrosis correlated significantly with interstitial markers in group I including interstitial alphaSMA (r=0.837, P=0.00) interstitial vimentin (r=0.929, P=0.00), interstitial apoptosis (r=0.807, P=0.00) and interstitial PCNA (r=0.617, P=0.01), while in group II it correlated with both interstitial and glomerular markers. In addition, the tubulo-interstitial ratio was significantly higher in group I in comparison with group II (P=0.024), with no difference between groups II and III. CONCLUSIONS: Although SN may start as glomerulopathy associated with increased mesangial cellularity, the interstitial rather than the glomerular markers of myofibroblastic differentiation and those of cell turnover are playing a crucial role in late stages of schistosomal, but not in non-schistosomal nephropathies.