Dina O. Abdulazim

Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: A review

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Stop chronic kidney disease progression: Time is approaching

Progression of chronic kidney disease (CKD) is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointerstitial disease. The chronic systemic inflammatory status and increased oxidative stress were also investigated. This inflammatory status influences the anti-senescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of inflammation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression.

Diabetic nephropathy: Time to withhold development and progression - A review

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FGF23 and inflammation

Systemic inflammation is a recognized feature in chronic kidney disease (CKD). The role of systemic inflammation in the pathogenesis of vascular calcification was recently settled. FGF23 was recently accused as a direct stimulus of systemic inflammation. This finding explains the strong association of FGF23 to vascular calcification and increased mortality among CKD.

Is Fibroblast growth factor 23 the leading cause of increased mortality among chronic kidney disease patients? A narrative review

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Vascular calcification: When should we interfere in chronic kidney disease patients and how?

Chronic kidney disease (CKD) patients are endangered with the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the fatalities. Cardiovascular calcifications affect most of the CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 and klotho deficiency were incriminated in the pathogenesis of vascular calcification through different mechanisms including their effects on endothelium and arterial wall smooth muscle cells. In addition, deficient klotho gene expression, a constant feature of CKD, promotes vascular pathology and shares in progression of the CKD. The role of gut in the etio-pathogenesis of systemic inflammation and vascular calcification is a newly discovered mechanism. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, different tools used to diagnose, the ideal timing to prevent or to withhold the progression of vascular calcification and the different medications and medical procedures that can help to prolong the survival of CKD patients.

Fibroblast growth factor-23 is a strong predictor of insulin resistance among chronic kidney disease patients

Abstract Insulin resistance (IR) is very common among chronic kidney disease (CKD) patients. Disturbance in mineral and bone metabolism (MBD) seems to play a role in the pathogenesis of insulin resistance. Fibroblast growth factor-23 (FGF23) is evolving as the most important link between MBD and many pathologic sequences of CKD. The aim was to evaluate IR in pre-dialysis CKD patients looking for a possible association to mineral metabolism among CKD patients. A total of 100 stage 3–5 CKD patients were selected beside 20 normal control subjects. Homeostatic model assessment of insulin resistance (HOMA-IR) was used to assess IR in selected cases. Both groups were compared for fasting blood glucose (FBG), fasting blood insulin (FBI), HOMA-IR, estimated glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), 25 hydroxy vitamin D (25 OH vit D), parathormone (PTH), and uric acid (UA). Correlation study between HOMA_IR and different studied parameters was performed. HOMA-IR is significantly higher in CKD (8.87 ± 3.48 vs. 3.97 ± 0.34 in CKD vs. control, respectively, p < .001). In addition CKD patients have significantly higher FGF23 (235 ± 22.96 vs. 139 ± 12.3 pg/mL, p < .001), PTH (76.9 ± 15.27 vs. 47.9 ± 2.52 pg/mL, p < .001), P (4.3 ± 0.67 vs. 3.6 ± 0.23 mg/dL, p < .001), and UA (5 ± 1.22 vs. 4.85 ± 0.48 mg/dL, p < .001) and significantly lower Ca (8.2 ± 0.3 vs. 8.9 ± 0.33 mg/dL, p < .001), and 25 (OH) vit D (17 ± 5.63 vs. 37 ± 3.43 ng/mL, p < .001). Stepwise linear regression analysis revealed that BMI, GFR, Ca, P, and FGF23 were the only significant predictors of HOMA IR. Increased IR in CKD is a consequence of the uremic status and is intimately associated with disturbed phosphate metabolism and FGF23. Further studies are needed to look for an underlying mechanism.

Serum 25-hydroxyvitamin D level is negatively associated with serum phosphorus level among stage 3a-5 chronic kidney disease patients

BACKGROUND Serum 25-hydroxyvitamin D (25(OH)D) negatively correlates with serum phosphorus level of stage 3a-5 chronic kidney disease (CKD) patients. So far, no explanation has been provided for this negative association. OBJECTIVE To confirm this negative association and determine if this relationship is mediated through other known co-morbid factors. CASES AND METHODS One hundred (57 male and 43 female) pre-dialysis stage 3a-5 CKD patients were selected. Estimated glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), 25(OH)D, parathyroid hormone (PTH), and intact fibroblast growth factor-23 (FGF23) were assessed. A correlation analysis between serum 25(OH)D and the different parameters studied was performed. Multivariate linear regression analysis was carried out to determine predictors of 25(OH)D. RESULTS The negative association between serum 25(OH)D and serum P was confirmed in univariate and multivariate correlation analysis. On the other hand, we failed to detect a significant association between 25(OH)D and serum FGF23. Serum P is the most important independent predictor of 25(OH)D in these patients (partial R2=0.15, p<0.0001). CONCLUSION Serum P is likely to have a direct negative impact on serum 25(OH)D. Further studies are needed to determine the underlying mechanism.

Vitamin D Deficiency as a Cause of Flank Pain

Introduction: Loin pain is a relatively common complaint seen in a variety of clinical settings. Many of these cases seek medical advice of urologists and nephrologists based on the impression that this pain originates from the urinary tract. In spite of the importance of diseases of the urinary tract as causes of loin pain, many of the patients presenting with this complaint are devoid of any urinary abnormalities. Methods: Differential diagnosis includes musculoskeletal, respiratory, gastrointestinal, neurologic and cutaneous causes. In this work, we present a series of 187 cases presenting to our center with loin pain that did not prove a renal cause. Results: During physical examination of these cases, tenderness over the lowermost ribs above the flank at the posterior and mid axillary lines was eminent. Within the laboratory and radiologic work-up performed to these cases, very low serum level of 25 (OH) vitamin D was a constant feature. Vitamin D replacement was associated with complete relief of the pain in most of these cases. Conclusion: The presence of tenderness over the costal margin rather than the renal angle proper should alert examining physician to the possibility of disease in the ribs. After exclusion of trauma as a cause of this pain and tenderness, estimation of vitamin D level is a mandate.

Recent Advances in Management of Diabetic Nephropathy

Diabetic nephropathy (DN) is not only the most common cause of end-stage renal disease world-wide but also increases the risk of mortality up to fourteen times compared to normoalbuminuric diabetic patients. After a long time of inertia, recent advances in the management of diabetes have added a valuable share to the effort of prevention and slowing the progression of DN. Beyond their hypoglycemic effects, dipeptidyl peptidase-4 inhibitors, and sodium glucose transporter 2 inhibitors have shown unique renoprotective mechanisms in both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Advances in this field included, in addition, the introduction of many anti-oxidant and anti-inflammatory agents that proved in experimental and in vitro studies to add significant impact on development and progression of DN. Most of these agents are still waiting for clinical studies to confirm their safety and efficacy. Beside their role in improving plans of management, the new discoveries have improved our understanding of the pathogenesis of DN. This review will cover the updates in established and potential therapeutic modalities that would improve the management of DN after discussing the pathogenic pathways that help in understanding the mechanism of action of these different treatments.