Faculty Bibliography

Acute and chronic kidney diseases occur after hematopoietic stem cell transplantation. These are caused by the transplant itself, and the complications of transplant. Recent estimates show that near 15% of subjects undergoing hematopoietic stem cell transplantation will develop chronic kidney disease, which is a complication rate that can affect outcome and reduce survival. Investigation of the causes of chronic kidney disease is needed, as are ways to prevent, mitigate, and treat it.

Chronic kidney disease (CKD) is a worldwide public health problem. Little is known about its burden in Africa. This paper reviews the knowledge of CKD in Kinshasa, summarizing four studies undertaken in the general population and traditional health system of Kinshasa. CKD was defined by either kidney damage (proteinuria> or =300 mg/day) or reduced kidney function (eGFR<60 ml/min/1.73 m(2)). In the general population, the prevalence of CKD all stage is 12.4 %. Our work shows also the high prevalence of proteinuria among subjects who do not have diabetes or hypertension, the lack of early detection and management of CKD risk factors in the traditional health care system leading to late referral or premature deaths, and the limits of renal replacement treatment. CKD affects young people in the DRC, in contrast to the United States, where CKD is more prevalent in older people. Major determinants of CKD in our studies were hypertension, diabetes, overweight, age, lower socioeconomic status, and Human immunodeficiency virus (HIV) infection. Glomerular nephropathy (mainly focal segmental glomerulosclerosis) remains the leading cause of end stage renal disease. An annual screening of the population for proteinuria and CKD risk factors is feasible and will, it is hoped, provide the basis for building a nationwide prevention strategy.

INTRODUCTION/BACKGROUND:Hypertension is an important risk factor for cardiovascular disease and its management requires improvement. New treatment strategies are needed. AIMS/OBJECTIVE:This review analyses one of these strategies, which is the development of effective and safe combination therapy. Indeed, at least two antihypertensive agents are often needed to achieve blood pressure control. Exforge((R)) (Novartis) is a new drug combination of the calcium channel blocker, amlodipine, and the angiotensin II receptor blocker, valsartan. EVIDENCE REVIEW/METHODS:The amlodipine/valsartan combination is an association of two well-known antihypertensive products with specific targets in cardiovascular protection, namely calcium channel blockade and antagonism of the renin-angiotensin-aldosterone system. This kind of association, with neutral metabolic properties and significant antihypertensive efficacy, could be a useful new antihypertensive product. Currently available data have shown that this new combination is well-tolerated and effective even in severe hypertension. CLINICAL VALUE/CONCLUSIONS:Clinical trials are ongoing for further assessment of the efficacy, compliance, and safety of this combination and its congeners. No data exist to prove that the amlodipine/valsartan combination is better than other antihypertensive strategies for cardiovascular or renal protection, but some trials with other combination therapies show such potential advantage.

Radiation exposures from accidents, nuclear detonations or terrorist incidents are unlikely to be homogeneous; however, current biodosimetric approaches are developed and validated primarily in whole-body irradiation models. A workshop was held at the Armed Forces Radiobiology Research Institute in May 2008 to draw attention to the need for partial-body biodosimetry, to discuss current knowledge, and to identify the gaps to be filled. A panel of international experts and the workshop attendees discussed the requirements and concepts for a path forward. This report addresses eight key areas identified by the Workshop Program Committee for future focus: (1) improved cytogenetics, (2) clinical signs and symptoms, (3) cutaneous bioindicators, (4) organ-specific biomarkers, (5) biophysical markers of dose, (6) integrated diagnostic approaches, (7) confounding factors, and (8) requirements for post-event medical follow-up. For each area, the status, advantages and limitations of existing approaches and suggestions for new directions are presented.

Victims of nuclear accidents or radiological terrorism are likely to receive varying doses of ionizing radiation inhomogeneously distributed over the body. Early biomarkers may be useful in determining organ-specific doses due to total body irradiation (TBI) or partial body irradiation. The authors used liquid chromatography and mass spectrometry to compare the effect of TBI and local kidney irradiation (LKI) on the rat urine proteome using a single 10-Gy dose of x-rays. Both TBI and LKI altered the urinary protein profile within 24 h with noticeable differences in gene ontology categories. Some proteins, including fetuin-B, tissue kallikrein, beta-glucuronidase, vitamin D-dependent calcium binding protein and chondroitin sulfate proteoglycan NG2, were detected only in the TBI group. Some other proteins, including major urinary protein-1, RNA binding protein 19, neuron navigator, Dapper homolog 3, WD repeat and FYVE domain containing protein 3, sorting nexin-8, ankycorbin and aquaporin were detected only in the LKI group. Protease inhibitors and kidney proteins were more abundant (fraction of total scans) in the LKI group. Urine protein (Up) and creatinine (Uc) (Up/Uc) ratios and urinary albumin abundance decreased in both TBI and LKI groups. Several markers of acute kidney injury were not detectable in either irradiated group. Present data indicate that abundance and number of proteins may follow opposite trends. These novel findings demonstrate intriguing differences between TBI and LKI, and suggest that urine proteome may be useful in determining organ-specific changes caused by partial body irradiation.

Hemodialysis patients have greater morbidity and mortality when they have a catheter rather than an arteriovenous fistula access. Catheter infection plays a significant role in this effect. Inflammation associated with dialysis catheter use could have an independent adverse effect on patient outcomes. Awareness and further study of the role of inflammation are needed.

Abstract Persistent, chronic oxidative injury may play a mechanistic role in late radiation injury. Thus antioxidants may be useful as mitigators of radiation injury. The antioxidants deferiprone, genistein and apocynin were tested in a rat radiation nephropathy model that uses single-fraction total-body irradiation (TBI) followed by syngeneic bone marrow transplant. Deferiprone was added to the drinking water at 1.0 or 2.5 g/liter, starting 3 days after the TBI. Urinary bleomycin-detectable iron, which could enhance production of oxygen radicals, was reduced in the rats on deferiprone compared to untreated rats, but deferiprone did not mitigate radiation nephropathy. Genistein added to the chow at 750 mg/kg starting immediately after TBI did not mitigate radiation nephropathy. Apocynin added to the drinking water at 250 mg/liter immediately after TBI did not mitigate radiation nephropathy. Thus three different types of antioxidants, when used at doses consistent with an antioxidant effect, had no mitigation efficacy against radiation nephropathy.

BACKGROUND:There is limited knowledge of Chronic Kidney Disease (CKD) among high risk populations, especially in the developing countries. We report our study of testing for CKD in at-risk subjects. METHODS:In a cross-sectional study, 527 people from primary and secondary health care areas in the city of Kinshasa were studied from a random sample of at-risk out-patients with hypertension, diabetes, obesity, or HIV+. We measured blood pressure (BP), blood glucose level, proteinuria, body mass index, and estimated glomerular filtration rate (eGFR by MDRD equation) using calibrated creatinine levels based on one random measurement. The associations between health characteristics, indicators of kidney damage (proteinuria) and kidney function (<60 ml/min/1.73 m2) were also examined. RESULTS:The prevalence of CKD in this study was 36%, but only 12% were aware of their condition. 4% of patients had stage 1 CKD, 6% stage 2, 18% stage 3, 2% stage 4, and 6% had stage 5. 24 hour quantitative proteinuria (>300 mg/day) was found in 19%. In those with the at-risk conditions, the % of CKD was: 44% in patients with hypertension, 39% in those with diabetes; 16% in the obese and 12% in those who were HIV+. 82% of those with a history of diabetes had elevated serum glucose levels at screening (>or= 126 mg/dl). Only 6% of individuals with hypertension having CKD had reduced BP to lower than 130/80 mmHg. In multivariate analysis, diabetes, proteinuria and hypertension were the strongest determinants of CKD 3+. CONCLUSION/CONCLUSIONS:It appears that one out of three people in this at-risk population has undiagnosed CKD and poorly controlled CKD risk factors. This growing problem poses clear challenges to this developing country. Therefore, CKD should be addressed through the development of multidisciplinary teams and improved communication between traditional health care givers and nephrology services. Attention to CKD risk factors must become a priority.