Gamal Saadi

Egypt, the single country with highest incidence of HCV infection in the world, has embarked on a government-sponsored mass treatment program using several combinations of DAAs. Recognizing the importance of extrahepatic manifestations, independently of the hepatic, a subcommittee was assigned to develop national guidelines for respective prioritizing indications and protocols. It evaluated the benefit of treating patients with different extrahepatic manifestations, and reviewed relevant clinical trials and guidelines concerning DAA combinations available in Egypt. The latter included Sofosbuvir plus either peg-interferon, Simeprevir, Ledipasvir or daclatasvir, and the Viekera family comprising paritaprevir/ritonavir + ombitasvir with (GT-1) or without (GT-4) Dasabuvir. Any of these protocols may be used with or without Ribavirin according to indication. A blueprint was subjected to peer debate in dedicated workshops in two national meetings and subsequently to an online professional review, eventually leading to a final report that was adopted by the health authorities. Seven compelling and 10 optional indications were identified for treating patients with predominantly extrahepatic manifestations. The former include kidney disease at different stages, cryoglobulinemic vasculitis and non-Hodgkin lymphoma. Selected treatment protocols, were encoded and their use was prioritized on the basis of evidence of efficacy and safety. We concluded that any of the studied protocols may be used, preferably with ribavirin, for 12-week treatment in all patients with extrahepatic manifestations without cirrhosis and with eGFR above 30 ml/min/1.73 sqm. Ribavirin should be included in protocols for treating patients with compensated cirrhosis. Daclatasvir-based protocols are recommended for decompensated cirrhosis, while the Viekera family is recommended in patients with eGFR < 30 ml/min/1.73 sqm, including those on dialysis. In kidney-transplanted patents, caution is due to avoidance of the pharmacokinetic interaction with the Cytochrome-P450 enzyme system, in-between immunosuppressive agents and most DAAs, particularly the Viekera family.

Background and Aim: Type 2 diabetes mellitus (DM) is the most common single cause of the end-stage renal disease (ESRD). Cyclophilin A (CyPA) is an 18-kD protein. The connection between diabetic nephropathy (DN) and the secreted form of CyPA (sCyPA) has been elucidated in this study that aims to investigate sCyPA correlation with renal dysfunction.

Materials and Methods: Thirty-four male adult Wistar rats weighing 180-220 g were used. Animals were divided into a study group and a control group, 17 rats in each. Streptozotocin (STZ) and nicotine amide were used to damage some pancreatic cells for induction of type 2 DM. Comparison was made between the study and the control groups. Moreover, a comparison was made between the members of the study group before and after induction of DN.

Results: The rat model that exhibited a higher concentration of urinary sCyPA was detected early in the eighth week. There was a significantly higher level of 24-h urinary CyPA in the study group compared to the control group (-value=0.004) and there was a significant elevation in the 24-h urinary Cyp-A in the study group after injection of STZ compared to the values before injection (-value <0.001). Immunohistochemical analysis of renal tissue revealed that the mean expression of CyPA was higher in the study group than in the control group. For the urinary 24-h CYP-A, using a cutoff of 1.15 ng/mL, the accuracy was 72.4%, sensitivity was (77.8%) and specificity was (67%).

Conclusion: According to this animal study, we proved that CyPA is a valuable marker for DN. It is a more sensitive, noninvasive and rapid biomarker for early detection of any renal affection in human diabetic patients.

Given the uncertainty regarding the relationship between donor cells at microchimeric levels and its influence on graft function and clinical outcome, we explored the extent and importance of donor microchimerism in kidney transplantation. Twenty patients with chronic kidney disease who had received allografts from living donors were studied. We examined peripheral whole blood samples from the recipients one month after the transplant, applying mitochondrial DNA variant-specific polymerase chain reaction (PCR) to identify and quantify donor cells in relation to allograft function and survival during three years of follow-up. Higher quantities of donor-derived cell microchimerism in the peripheral blood correlated with better graft function in the early postoperative period at 1 month (R  = .536, p = .001) and predicted improved graft function 1 year following the transplant (R  = .430, p = .008). Furthermore, early post-transplant quantities of donor cell microchimerism were an important predictor of improved kidney function 3 years after transplantation (R  = .397, p = .021). However, donor cell microchimerism failed to predict patient and graft survival after 3 years (odds ratio = 0.536, p = .860). Our findings suggest that donor cell microchimerism plays an immunoregulatory role in kidney transplantation and contributes to donor-specific immune hypo-responsiveness and graft acceptance.

Hepatitis C virus (HCV) infection is an important cause of major morbidities including chronic liver disease, liver cancer, and acute kidney injury (AKI) as well as chronic kidney disease (CKD). HCV can affect kidney health; among CKD and AKI patients with HCV infection, the clinical outcomes are worse. The prevalence of HCV infection is exceptionally high among dialysis and kidney transplant patients throughout the globe. It is estimated that 5% to 25% or more of dialysis dependent patients are affected by chronic HCV, based on the region of the world. Almost half of all deaths in CKD patients, including HCV-infected patients, are due to cardiovascular disease, and HCV infected patients have higher mortality. Given the importance and impact of the HCV epidemic on CKD and global kidney health, and the status of Egypt as the nation with highest prevalence of HCV infection in the world along with its leading initiatives to eradicate HCV, the International Federation of Kidney Foundations (IFKF) convened a consensus conference in Cairo in December 2017. This article reflects the opinions and recommendations of the contributing experts and reiterates that with the current availability of highly effective and well tolerated pharmacotherapy; CKD patients should be given priority for treatment of HCV, as an important step towards the elimination of viral hepatitis as a public health problem by 2030 according to World Health Organization and IFKF. Every country should have an action plan with the goal to improve kidney health and CKD patient outcomes.

Living with chronic kidney disease (CKD) is associated with hardships for patients and their care partners. Empowering patients and their care partners, including family members and friends involved in their care, may help minimize the burden and consequences of CKD-related symptoms to enable increased life participation. There is a need to broaden the focus on living well with kidney disease and reengagement in life, including emphasis on the patient being in control. The World Kidney Day (WKD) Joint Steering Committee has declared 2021 the year of "Living Well with Kidney Disease" in an effort to increase education about and awareness of the important goal of patient empowerment and life participation. This calls for the development and implementation of validated patient-reported outcome measures to assess and address areas of life participation in routine care. It could be supported by regulatory agencies as a metric for quality care or to support labeling claims for medicines and devices. Funding agencies could establish targeted calls for research that address the priorities of patients. Patients with kidney disease and their care partners should feel supported to live well through concerted efforts by kidney care communities, including during pandemics. In the overall wellness program for patients with kidney disease, the need for prevention should be reiterated. Early detection with prolonged course of wellness despite kidney disease, after effective secondary and tertiary prevention programs, should be promoted. WKD 2021 continues to call for increased awareness of the importance of preventive measures across populations, professionals, and policy makers, applicable to both developed and developing countries.

BACKGROUND: Vitamin D has shown an immune-modulatory effect in different studies. Vitamin D stimulates Tregs and inhibits Th17 cells. The immune-modulatory role of vitamin D in chronic kidney disease (CKD) and renal transplant patients is unclear. We measured whether different serum levels of vitamin D were associated with an increased or decreased presence of lymphocyte subsets including Treg and Th17 cells in end-stage renal disease (ESRD) and renal transplant recipients.

METHODS: Eighty-seven renal transplant recipients and 53 end-stage renal disease (ESRD) patients were enrolled in this study. The absolute counts of CD4+ and CD8+ T, CD16+ CD56+ NK, CD19+ B, CD4+ CD25+ CD127- Foxp3+ (Tregs), Helios+ Tregs, CD38+ Tregs, and CD4+ CD17+ (Th17) cells were analyzed in peripheral blood in both patient groups. In addition, serum 25 (OH) D, 1, 25 (OH) D, IL-6, IL-17, IL-23, and TGF-β were measured. The association between lymphocyte subset counts and 1, 25 (OH) D or 25 (OH) D was studied, as was the association between serum IL-6, IL-17, IL-23, or TGF-β and 1,25 (OH) D or 25 (OH) D.

RESULTS: Serum 25 (OH) D and 1,25 (OH) D levels were not independently associated with peripheral CD4+ T, CD19+ B, CD16+ CD56+ NK, Treg, or Th17 cell counts. In contrast to serum 25 (OH) D, serum1, 25 (OH) D was positively associated with CD8+ T cells counts in renal transplant recipients.

CONCLUSION: Our findings indicate low utility of serum 25 (OH) D and 1, 25 (OH) D levels in predicting a change in lymphocyte subset counts in ESRD and renal transplant patients.

OBJECTIVES: Donor specific antibodies (DSA) and a positive cross-match are contraindications for kidney transplantation. Trials of allograft transplantation across the HLA barrier have employed desensitization strategies, including the use of plasmapheresis, intravenous immunoglobulins, anti-B-cell monoclonal antibodies and splenectomy, associated with high-intensity immunosuppressive regimens. Our case 1 report suffered from repeatedly positive lymphocyte cross match after 1st renal transplantation. Graft nephrectomy could not correct the state of sensitization. Splenectomy was done in a trial to get rid of the antibody producing clone. Furthermore plasmapheresis with low dose IVIG could not as well revert the state of sensitization for the patient.

MATERIAL AND METHODS: About 50 millions donor specific MSCs were injected to the patient.

RESULTS: MSCs transfusion proved to be the only procedure which could achieve successful desensitization before performing the second transplantation owing to their immunosuppressive properties.

CONCLUSION: This case indicates that DS-MSCs is a potential option for anti-HLA desensitization. In cases 2 and 3 IV DS-MSCs transfusion was selected from the start as a successful line of treatment for pre renal transplantation desensitization to save other unnecessary lines of treatment that were tried in case 1.

The increasing demand for solid organs has necessitated the use of ABO and Rhesus (Rh) D minor mismatched transplants. The passenger lymphocyte syndrome (PLS) occurs when donor lymphocytes produce antibodies that react with host red blood cell (RBC) antigens and result in hemolysis. Our aim was to evaluate prospectively the role of PLS in post transplant anemia and hemolysis in ABO and RhD minor mismatched recipients of liver and kidney grafts and to study the association of PLS with donor lymphocyte microchimerism. We examined 11 liver and 10 kidney recipients at Day +15 for anemia, markers of hemolysis, direct antiglobulin test and eluates, and serum RBC antibodies. Microchimerism was determined in peripheral blood lymphocytes by genotyping of simple sequence length polymorphisms encoding short tandem repeats. Immune hemolytic anemia and anti-recipient RBC antibodies were observed in 2 out of 11 liver (18.2%) and 2 out of 10 kidney (20%) transplants. RBC antibody specificity reflected the donor to recipient transplant, with anti-blood group B antibodies identified in 2 cases of O to B and 1 case of A to AB transplants while anti-D antibodies were detected in 1 case of RhD-negative to RhD-positive transplant. Donor microchimerism was found in only 1 patient. In conclusion, passenger lymphocyte mediated hemolysis is frequent in minor mismatched liver and kidney transplantation. Recognizing PLS as a potential cause of post transplant anemia may allow for early diagnosis and management to decrease the morbidity and mortality in some patients.

Patients with chronic kidney disease (CKD) frequently experience unpleasant symptoms. These can be gastrointestinal (constipation, nausea, vomiting and diarrhoea), psychological (anxiety and sadness), neurological (lightheadedness, headache and numbness), cardiopulmonary (shortness of breath and oedema), dermatological (pruritus and dry skin), painful (muscle cramps, chest pain and abdominal pain) or involve sexual dysfunction, sleep disorders and fatigue. These symptoms often occur in clusters, with one of them as the lead symptom and others as secondary symptoms. Uraemic toxins (also called uremic toxins) are often considered to be the main cause of CKD-associated symptom burden, but treatment of uraemia by dialysis often fails to resolve them and can engender additional symptoms. Indeed, symptoms can be exacerbated by comorbid conditions, pharmacotherapies, lifestyle and dietary regimens, kidney replacement therapy and ageing. Patients with kidney disease, including those who depend on dialysis or transplantation, should feel actively supported in their symptom management through the identification and targeting of unpleasant symptoms via a tailored palliative care approach. Such an approach may help minimize the burden and consequences of kidney disease, and lead to improved patient outcomes including health-related quality of life and better life participation.

Pediatric kidney transplantation is a multidisciplinary therapy that needs special consideration and experience. In this study, we aimed to present CUCH experience; over a 10-year period, as a specialized center of kidney transplantation in children. We studied 148 transplantations performed at a single center from 2009 to 2018. Pretransplant and follow-up data were collected and graft/patient survival rates were evaluated. A total of 48 patients developed at least one rejection episode during 688 patient-years of follow-up. Infections, recurrence of original disease, and malignancy were the most important encountered medical complications (20%, 2%, and 1.4%, respectively). One-year patient survival was 94.1%, while graft and patient survival was 91.9%. Graft/patient survival at 5, 7, and 9 years was 90%, 77%, and 58%, respectively. Infections were the main cause (69%) of mortality. Death with a functioning graft and CR were the main causes of graft loss (48% and 33%, respectively). Pediatric kidney transplantation in Egypt is still a challenging yet successful experience. Rejections and infections are the most frequent complications. Short-term outcomes surpass long-term ones and graft survival rates are similar to the international standard.

BACKGROUND: Polyomavirus nephropathy (PVN) mainly caused by BK polyomavirus (BKPyV) remains the most common productive viral infection of the kidney in immunosuppressed patients. The diagnosis of PVN is based on the detection of BK viruria and BK viremia in conjunction with histological findings in the graft biopsy.

METHODS: Our study was aimed to estimate the prevalence of productive BKPyV infection among renal transplant patients within the first year post-transplant and identify those at risk of developing PVN. Our cross-sectional study was conducted on 134 kidney transplant patients. Evidence of BKPyV replication was assessed by viral quantification of blood and urine samples of studied patients using a quantitative real-time polymerase chain reaction (Q-PCR)PCR), detection of decoy cells in urine cytology smears, histological examination of graft biopsies from Q-PCR BKPyV-positive patients, and immunohistochemical staining by simian virus 40 (SV40) antibody.

RESULTS: Significant BKPyV infection was prevalent in 8% (n = 11) of our patients, with a peak of BKPyV infection about 8 months post transplant. BKPyV viral load by Q-PCR assay in these patients varied from 1350 to 20,000,000 (1.35 × 10(3) to 2 × 10(7) ) copies/mL for urine samples and 935 to 18,920 (9.35 × 10(2) to 1.89 × 10(4) ) copies/mL for blood samples. All the 11 patients were positive for decoy cells but only 3 developed PVN based on histology and positive SV40 staining. BKPyV infection was more prevalent in older patients. All patients responded to reduction in their immunosuppressive regimens, apart from 2 patients who required replacement of calcineurin inhibitors-based regimen with mammalian target of ramapycin inhibitors with an overall good response.

CONCLUSION: Protocol screening programs based on detection of viral replication by viruria, viremia, and decoy cells in urine are necessary to shed light on patients with high virus replication and hence increased risk of developing PVN, and to allow early diagnosis and intervention.

This work evaluated risk factors predisposing to toxoplasmosis in chronic renal failure patients and renal transplant recipients. The present study included 91 cases classified according to their renal status into four groups; control group, renal failure patients not on haemodialysis, renal failure patients on regular haemodialysis and renal transplant recipients group. The age groups (< 20) and (30-) had the highest positivity for anti-Toxoplasma IgG & IgM antibodies in comparison to the other age groups. The results showed no sex difference in positivity rate for anti-Toxoplasma IgG & IgM in groups. There was no significant difference between groups regarding risk factors for contracting toxoplasmosis, clinical presentation suggestive of toxoplasmosis and diabetes mellitus. There was significant difference between all groups as regarding intake of immunosuppressive drugs and blood transfusion.

Toxoplasma gondii antibodies were detected in 78 patients with renal disease by ELISA. Patients were classified according to the renal status; chronic renal failure patients not on haemodialysis (G1 = 19), chronic renal failure patients on regular haemodialysis (G2 = 30), renal transplant recipient (G3 = 29) and 13 normal controls. Anti-Toxoplasma IgG & IgM antibodies were 36.8% & 10.5% in renal failure patients not on haemodialysis, 56.7% &16.7% in patients on regular haemodialysis and 69% & 24.1% in renal transplant recipients versus 23.1% & 0% in controls with statistical significant difference for Toxoplasma IgG antibodies only. Anti-Toxoplasma IgG antibodies levels of G3 were lower than that of G1. It was observed that the more the exposure to dialysis, the more the risk of toxoplasmosis. It was found that 85.71% of renal transplant recipient seropositive cases for anti-Toxoplasma IgM antibodies were detected in one year post-transplantation and 14.28% of cases after the first year of transplantation.

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.