Ahmed Fayed

Vascular calcification (VC) is a well-known complication in patients with chronic kidney disease (CKD). Keeping in mind, the end goal to assess the genuine effect of mineral bone disease in the pathogenesis of blood vessel calcification during the pre-dialysis course of CKD, we assessed the prevalence and extent of abdominal aortic calcification (AAC) in nondiabetic CKD patients recently starting hemodialysis (HD). Eighty-one patients with end-stage renal disease beginning HD over a one-month period were selected. They underwent a detailed clinical examination and laboratory evaluation, including serum calcium, phosphorus, parathyroid hormone, fibroblast growth factor (FGF-23), and alkaline phosphatase were measured, and spiral computed tomography was performed to evaluate AAC score. AAC was present in 64 patients (79%). There was a significant correlation between the AAC score and age (r = 0.609, P <0.001) and FGF-23 (r = 0.800, P <0.001). This study suggests that the prevalence and extent of AAC are critical in incident HD patients. Serum FGF-23 level is the sole statistically significant correlate of AAC in these patients.

OBJECTIVE: Sclerostin is an osteocyte-derived glycoprotein which inhibits the canonical Wnt pathway essential for osteoblastic activity decreasing bone formation. Its potential role in rheumatoid arthritis (RA) pathogenesis was highlighted by experimental studies. Here we measured the serum sclerostin in RA patients and evaluated its relationship with disease activity and damage.

METHODS: One hundred RA patients and 80 age and sex-matched healthy controls were enrolled in the study. Bone biomarkers were evaluated for all participants including total calcium, phosphorus, alkaline phosphatase, 25-hydroxy vitamin D, and intact parathyroid hormone, in addition to fibroblast growth factor-23 (FGF23) and serum sclerostin. For RA patients, carotid intima-media thickness, brachial artery flow dilatation, and musculoskeletal ultrasonography using ultrasonography-7 joint score were done, and DAS28-ESR was calculated.

RESULTS: Median serum sclerostin in our patients was 186.5 ± 22.7 pg/ml which was significantly higher than in controls 60.6 ± 7.1 pg/ml (p < 0.002). Serum sclerostin showed no correlation with disease activity, bone erosions, carotid intima-media thickness, brachial flow dilatation, and the examined bone biomarkers. However, it had a strong correlation with FGF23 (r coefficient 0.988, p < 0.000).

CONCLUSION: Although serum sclerostin was elevated in RA patients, it could not be used as a prognostic marker for disease activity, bone erosions or atherosclerosis.Key Points• Serum sclerostin may not reflect changes in the joint microenvironment being not correlated with ultrasonography-detected synovitis or erosions.• Serum sclerostin was elevated in RA patients irrespective to their age or gender.• The positive correlation with FGF23 may provide evidence for sclerostin contribution in bone demineralization in RA patients.

INTRODUCTION: Arterial calcification (AC) is a common complication in chronic kidney disease (CKD) patients that starts to develop before these patients need renal replacement therapy. In these patients, calcification can involve tunica intima or tunica media. This study has looked for the prevalence, severity, and distribution of arterial wall calcification in incident hemodialysis patients through intraoperative arterial biopsy obtained during creation of arteriovenous vascular access for hemodialysis.

METHODOLOGY: One hundred and seventy-two stage 5 CKD adults (98 male and 74 female) were included. Beside histopathology of the obtained arterial samples, all these cases were tested for serum calcium (Ca), phosphorus (P), alkaline phosphatase, uric acid, parathormone (PTH), fibroblast growth factor 23 (FGF23), and 25 hydroxy vitamin D.

RESULTS: Eighty six (50%) of the cases had AC (group I); 29 (17%) as intimal (subgroup Ii), 36 (21%) as medial (subgroup Im), while 21 (12%) had both intimal and medial calcification (subgroup Iim). Eighty-six patients (50%) were devoid of calcification (group II). Apart from the significantly higher serum level of PTH in group I, statistical analysis failed to disclose significant difference in any of the other studied parameters between the 2 groups. On the other hand, there were significant differences in serum P, Ca × P product, serum PTH, and FGF23 between patients according to intensity of calcification.

CONCLUSION: Half of incident hemodialysis CKD patients have developed AC mainly in tunica media. Discrepancy in serum P can have an impact on calcification intensity.

OBJECTIVE: Sclerostin is an osteocyte-secreted protein that downregulates bone formation by blocking the Wnt/β-catenin signaling pathway. Sclerostin can be induced by inflammation, and high levels have been reported in patients with proteinuria and renal impairment. Studies evaluating the role of sclerostin in systemic lupus erythematosus (SLE) patients are scarce. This study aims to measure serum sclerostin in SLE patients and correlate its level with bone biomarkers and disease activity, particularly in lupus nephritis and arthritis. Finally, we evaluated factors that may predict sclerostin concentrations.

METHODS: This cross-sectional, case-control study was conducted from May 2017 to April 2018. Serum sclerostin was measured by enzyme-linked immunosorbent assay in 100 SLE patients, including 50 patients with current lupus nephritis and 27 patients with current arthritis, as well as in 50 healthy controls. Correlation analysis of serum sclerostin with demography, bone biomarkers, and disease activity in SLE patients was carried out.

RESULTS: Sclerostin levels were significantly elevated in SLE patients, particularly those with lupus nephritis, compared with healthy controls. Higher levels were identified in patients without arthritis compared with those with; however, the former group had more proteinuria and renal impairment. Significant correlations were observed between sclerostin levels and serum creatinine, proteinuria, consumed C3 and C4 complement, and corrected Ca. Using multiple linear regression, proteinuria was the only significant predictor for serum sclerostin in SLE patients.

CONCLUSIONS: This study is the first to report that serum sclerostin is associated with proteinuria in SLE patients and could be used as a valuable biomarker for lupus nephritis.

Acute kidney injury (AKI) occurs in up to 50% of patients admitted to the intensive care units. Fibroblast growth factor 23 (FGF23), which plays an important role in regulating phosphate, rises early in AKI. Few studies were conducted to correlate the level of FGF23 and adverse outcomes in AKI. The study was conducted on 30 participants with AKI, which was defined according to AKI network criteria, admitted to the Critical Care Department, Kasr El Aini Hospital, Cairo University between July 2016 and May 2017, and serum FGF23 was measured within 24 h of AKI onset to correlate the level of FGF23 with mortality and need for renal replacement therapy (RRT). Enrollment FGF23 levels were significantly higher among patients who died than in the survival group (mean level: 544.2 vs. 59.3 pg/mL, P = 0.004). Furthermore, FGF23 levels were significantly higher in patients who needed RRT than in other participants (mean level: 529.5 vs. 285.11 pg/mL, P = 0.04). There was a statistically significant positive relationship between FGF23 level and sequential organ failure assessment score (P = 0.03). In patients with AKI, higher FGF23 levels are associated with increased risk of mortality and need for RRT.

Rheumatoid arthritis (RA) is accompanied by a variety of nephropathies. It is often difficult to distinguish between disease-associated and drug-associated renal diseases. Three hundred and seventy-six RA patients with renal involvement were included in our study; they were subjected to full history and clinical examination, kidney function, 24-h urinary protein, and kidney biopsy. All our patients were on methotrexate, low dose steroids, and nonsteroidal anti-inflammatory drugs, in addition to the previous medications. About 79.3%, 20.7%, 6.9%, and 5.9% of our patients were on leflunomide, hydroxychloroquine, etanercept, and infliximab, respectively. Renal presentation was in the form of nephrotic syndrome (33.5%), persistent subnephrotic proteinuria (12.2%), persistent proteinuria and recurrent hematuria (13.3%), acute nephritis (23.9), recurrent hematuria (7.4%), and creatinine >1.5 mg/dL (10.6%). Renal biopsies were glomerular amyloidosis (28.1%), mesangioproliferative (19.1%), membranous (6.1%), crescent (16.8%), focal segmental glomerulosclerosis (18.6%), and minimal changes (11.7%). There was a statistically significant difference in the incidence of membranous nephritis between patients who took leflunomide, and hydroxychloroquine and those did not. Etanercept in our study seems not to be related to any form of renal involvement, while infliximab is related to focal segmental sclerosis and amyloidosis of tubulointerstitial type. Kidney involvement in RA is not a rare complication. Any type of histopathological changes can be present, with amyloidosis on top of the list. Hydroxychloroquine and leflunomide are accused in membranous nephropathy. Infliximab is associated with focal segmental sclerosis and amyloidosis of tubulointerstial type, and etanercept appear to be safe as regards kidney affection.

INTRODUCTION: Podocyte injury and subsequent excretion in urine play a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). Quantification of messenger RNA expression in urinary sediment by real-time PCR is emerging as a noninvasive method of screening DN-associated biomarkers. We aimed to study the expression of podocyte-associated genes in urinary sediment and their relation to disease severity in type 2 diabetic Egyptian patients with diabetic nephropathy.

METHOD: ology: Sixty patients with type 2 diabetes mellitus were recruited in addition to twenty non diabetic healthy volunteers. Relative mRNA abundance of nephrin, podocalyxin, and podocin were quantified, and correlations between target mRNAs and clinical parameters were examined.

RESULTS: The urinary mRNA levels of all genes studied were significantly higher in diabetics compared with controls (p < 0.001), and mRNA levels increased with DN progression. Urinary mRNA levels of all target genes positively correlated with both UAE and HbA. The expression of nephrin, podocalyxin, and podocin mRNA correlated with serum creatinine {(r = 0.397, p value = 0.002), (r = 0.431, p value = 0.001), (r = 0.433, p value = 0.001) respectively}.

CONCLUSION: The urinary mRNA profiles of nephrin, podocalyxin, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN.

Low serum 25 hydroxyvitamin D (25 OH D) is common among chronic kidney disease (CKD) patients. This cross-sectional study is looking for the different factors associated with serum 25 OH D among pre-dialysis CKD. 1624 adult stage 3-5 CKD patients were studied beside 200 normal control subjects. All candidates were tested for body mass index (BMI), estimated glomerular filtration rate (eGFR), calcium (Ca), phosphorus (P), parathormone (PTH), 25 OH D, albumin, and uric acid (UA), and urine albumin/creatinine ratio (ACR). Multivariate linear regression analysis was done to determine predictors of 25 OH D. 98.6% of CKD patients have inadequate level of 25 OH D vs 48% of normal subjects. Serum 25 OH D was significantly lower in CKD patients (mean ± S.D = 16.54 ± 5.8 vs 37.79 ± 3.58 ng/mL for CKD vs control group respectively,  < .001). Serum level of 25 OH D has significant positive correlation with Ca ( = 0.337,  < .001), and significant negative correlation with P, PTH, UA, and ACR ( = -0.440, -0. 679, -0.724, and -0.781respectively,  < .001 in all). The independent predictors of 25 OH D were Ca, P, UA, PTH, and ACR (R square = 0.7, β = -0.087, -0.226, -0.313, -0.253, and -0.33 respectively,  < .001 in all). In conclusion, pre-dialysis CKD patients frequently suffer low 25 OH D. Among the different abnormalities related to CKD, urine albumin excretion rate and UA are the most important predictors of 25 OH D in these patients.

Currently, there is no available data about Vitamin D status among Egyptian chronic kidney disease (CKD) patients. This cross-sectional study is looking for the prevalence of Vitamin D deficiency among Stage 3a-5 CKD Egyptian patients and its possible associations. We studied 1624 Stage 3a-5 CKD adults (689 males and 935 females) together with 200 normal control persons. All the recruited candidates were tested for body mass index (BMI); serum levels of blood urea nitrogen, creatinine, calcium (Ca), phosphorus (P), parathyroid hormone (PTH), 25 hydroxy vitamin D (25(OH)D), albumin, and uric acid (UA); urine albumin/creatinine ratio (ACR), and estimated glomerular filtration rate. The optimal level of Vitamin D was encountered in only 1.4% of CKD patients versus 52% of the normal controls. A total of 1107 (68.2%) CKD patients versus 23 (11.5%) controls had serum 25(OH)D <20 ng/mL (mean ± standard deviation = 16.8 ± 5.8 versus 37.3±7.6 ng/mL for CKD versus control group, respectively, P <0.001). There was a highly statistically significant positive correlation between serum 25(OH)D and serum Ca (r = 0.299, P <0.001) and a highly statistically significant negative correlation between serum 25(OH)D on the one hand and serum P, serum PTH, serum UA, and urine ACR on the other hand (r = -0.46, -0.69, -0.73, and -0.8, respectively, P <0.001). Vitamin D deficiency is very common among Egyptian CKD patients. Serum P, UA, and urine ACR ratio are the most important variables which are found to be negatively associated with serum 25(OH)D.

INTRODUCTION: The side effects profile of the new direct--acting antivirals for the treatment of hepatitis C virus (HCV) is not fully elucidated.

OBJECTIVE: In this cross-sectional study, we aim to describe the incidence and characteristics of a novel observation of de novo renal cryoglobulinemic glomerulonephritis after successful treatment with DAA.

METHODOLOGY: A total of 12,985 Hepatitis C Patients (genotype IV) received the new DAA. After successful treatment, patients with deranged renal functions or proteinuria were referred to the nephrology department for assessment. The clinical manifestations ranged from lower limb edema to the development of purpura skin lesions. Cryoglobulins were tested in the serum using the PCR detection.

RESULTS: Fifty patients had detectable de novo cryoglobulins in the serum. The most common type in renal biopsies was membranoproliferative glomerulonephritis (52%) and chronic kidney disease (CKD) developed in 46% of cases.

CONCLUSION: De novo cryoglobulinemic glomerulonephritis and progression to CKD may rarely complicate successful treatment of HCV using direct-acting antivirals.

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.

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 R=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.

BACKGROUND AND STUDY AIM: Renal complications are frequent extraintestinal manifestations in inflammatory bowel disease (IBD). We aimed in our study to describe the spectrum of renal affection in our IBD patients.

PATIENTS AND METHODS: This study is a retrospective analysis of renal biopsies done for IBD patients who developed renal diseases, at Cairo University Hospital, from June 2005 to Jan. 2016. Results : Among 896 IBD patients, 218 patients (24.3%) developed renal affection. The onset of renal disease mandated renal biopsy at 5.6 ± 7.4 years after IBD diagnosis. Nephrotic range proteinuria was the most common indication for a renal biopsy [81 (37.15%) patients]. Amyloidosis was the most common renal pathological diagnosis [56 patients (25.7%)] followed by immunoglobulin A (IgA) nephropathy [35 patients (16.1%)], focal segmental glome- rulosclerosis (FSGS) [32patients (14.7%)], crescentic glomerulonephritis (CGN) [32 patients (14.7%)], membranous nephropathy (MN) [18 patients (8.25%)], minimal change disease [17 patients (7.7%)], chronic interstitial nephritis (CIN) [10 patients (4.6%)], acute tubular necrosis (ATN) [8 patients (3.7%)], thrombotic microangiopathy (TMA) [6 patients (2.75%)], and acute interstitial nephritis (AIN)[4 patients (1.8%)]. Variable renal histopathology diagnoses did not correlate with age, duration of IBD diagnosis, or drugs used for IBD treatment. Crescentic GN was significantly correlating with ASCA, ANCA-p, and ANCA-c in serum.

CONCLUSION: Amyloidosis is a common renal pathological diagnosis in our patients, and is followed by IgA nephropathy, and FSGS.

Therapeutic plasma exchange is used in treating different immunological and non-immunological diseases. We analyzed the outcome of 308 patients treated by 1783 membrane plasma exchange sessions from January 2011 until January 2017 at Cairo University Hospital. Thrombotic microangiopathies were the commonest indication [73 (23.7%) patients] with response in 63/73 patients (86.3%), followed by systemic vasculitis with pulmonary-renal involvement [40(13%) patients] with recovery in 32/40 patients (80.0%), Guillain-Barré syndrome [39(12.7%) patients] with recovery in 30/39 patients (76.9%), myasthenia gravis [31(10.1%) patients] with response in 26/31 patients (83.9%), and catastrophic antiphospholipid syndrome [28(9.1%) patients] with recovery in only 6/28 patients (21.4%). Complications included hypotension [276/1783 (15.5%) sessions], hypocalcemia [26/308 (8.5%) patients], and 37/308 (12%) patients died. Sepsis caused mortality in 29/37 (78.4%) of patients. In conclusion, our therapeutic plasma exchange experience shows a favorable outcome for thrombotic microangiopathies, systemic vasculitis, myasthenia gravis, and Guillain-Barré syndrome. Sepsis was the leading mortality cause.

Therapeutic plasma exchange is used in treating different immunological and non-immunological diseases. We analyzed the outcome of 308 patients treated by 1783 membrane plasma exchange sessions from January 2011 until January 2017 at Cairo University Hospital. Thrombotic microangiopathies were the commonest indication [73 (23.7%) patients] with response in 63/73 patients (86.3%), followed by systemic vasculitis with pulmonary-renal involvement [40(13%) patients] with recovery in 32/40 patients (80.0%), Guillain-Barré syndrome [39(12.7%) patients] with recovery in 30/39 patients (76.9%), myasthenia gravis [31(10.1%) patients] with response in 26/31 patients (83.9%), and catastrophic antiphospholipid syndrome [28(9.1%) patients] with recovery in only 6/28 patients (21.4%). Complications included hypotension [276/1783 (15.5%) sessions], hypocalcemia [26/308 (8.5%) patients], and 37/308 (12%) patients died. Sepsis caused mortality in 29/37 (78.4%) of patients. In conclusion, our therapeutic plasma exchange experience shows a favorable outcome for thrombotic microangiopathies, systemic vasculitis, myasthenia gravis, and Guillain-Barré syndrome. Sepsis was the leading mortality cause.

Aim We aim to describe the pattern of response to treatment in a cohort of Egyptian lupus nephritis (LN) patients and to define variable prognostic factors. Methods We retrospectively analyzed records of 928 systemic lupus erythematosus (SLE) patients (898 females, 30 males) with biopsy-confirmed LN seen between 2006 and 2012 at Cairo University hospitals. Results Our study involved 928 SLE patients with a mean age of 26.25 ± 6.487 years, mean LN duration at time of renal biopsy 6.48 ± 4.27 months, mean SLEDAI 28.22 ± 11.7, and mean follow-up duration of 44.14 ± 17.34 months. Induction treatment achieved remission in 683 patients. Remission was achieved in all 32 patients with class II LN, compared to 651/896 (72.7%) patients in classes III, IV, and V. Induction by intravenous (IV) cyclophosphamide achieved response in 435/575 (75.7%) patients, while induction by mycophenolate mofetil (MMF) resulted in response in 216/321 (67.3%) patients ( p = 0.0068). Nephritic flares were least observed when MMF was used for maintenance (30/239 (12.6%) patients), compared to 71/365 patients (19.5%) ( p = 0.0266) when azathioprine (AZA) was used, and 22/79 patients (27.8%) ( p = 0.002) with IV cyclophosphamide. Class IV LN, high chronicity index, presence of crescents, and interstitial fibrosis in biopsies were all associated with chronic kidney disease (CKD) development eventually ( p < 0.001, p = 0.005, p = 0.012, and p = 0.031, respectively). By the end of the study duration, 305 (32.7%) patients had CKD. Logistic regression detected that high baseline serum creatinine, failure to achieve remission, hypertension, and nephritic flare were the main risk factors for poor renal outcome ( p < 0.001, p < 0.001, p = 0.004, and p < 0.001, respectively). The 5 years' mortality was 69 (7.4%) patients with sepsis being the main cause of death. Conclusion IV cyclophosphamide superseded as induction treatment, while MMF was the best maintenance treatment. High serum creatinine, hypertension, and nephritic flare were the main risk factors for poor renal outcome.

Our study aimed to obtain a comprehensive review of the incidence of biopsy-proven glomerulonephritis (GN) at the Cairo University Hospitals, Egypt, over the last five years. We analyzed the clinical and pathological data of all renal biopsy samples that were performed during the period from July 2003 to July 2008. Renal biopsy samples of 924 patients were referred for pathological assessment during the period of the study [437 male and 487 female patients; their mean age was 26.5 ± 14.6 years (range: 2.5-71 years)]. Focal segmental glomerulo-nephritis was the most frequent cause of primary GN (21.21%), followed by mesangial proliferative GN (18.93%), diffuse proliferative GN (13.96%), focal proliferative GN (12.77%) and membranous GN (10.93%). The results could be explained by the high incidence of lupus nephritis among the study subjects as well as the relatively young age of the study group.