"Hyperglycemic Memory": Observational Evidence to Experimental Inference.

Several epidemiological studies have appreciated the impact of "duration" and "level" of hyperglycemia on the initiation and development of chronic complications of diabetes. However, glycemic profiles could not fully explain the presence/absence and severity of diabetic complications. Genetic issues and concepts of "hyperglycemic memory" have been introduced as additional influential factors involved in the pathobiology of late complications of diabetes. In the extended phase of significant diabetes randomized, controlled clinical trials, including DCCT/EDIC and UKPDS, studies have concluded that the quality of glycemic or metabolic control at the early time around the diabetes onset could maintain its protective or detrimental impact throughout the following diabetes course. There is no reliable indication of the mechanism by which the transient exposure to a given glucose concentration level could evoke a consistent cellular response at target tissues at the molecular levels. Some biological phenomena, such as the production and the concentration of advanced glycation end products (AGEs), reactive oxygen species (ROS) and protein kinase C (PKC) pathway activations, epigenetic changes, and finally, the miRNAs-mediated pathways, may be accountable for the development of hyperglycemic memory. This work summarizes evidence from previous experiments that may substantiate the hyperglycemic memory soundness by its justification in molecular terms.

Estimating Patient Survival and Risk of End-Stage Kidney Disease in Patients With Autosomal Dominant Polycystic Kidney Disease in Iran.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disease that can affect several organs. The clinical course of the disease varies among patients; some never become symptomatic, and others reach end-stage kidney disease (ESKD) in the 5th decade of their life. METHODS: This historical cohort study was conducted on ADPKD patients to investigate kidney and patient survival rates and related risk factors in Iran. Survival analysis and risk ratio calculation were performed using the Cox proportional hazards model, Kaplan- Meier method, and log-rank test. RESULTS: Among the 145 participants, 67 developed ESKD, and 20 died before the end of the study period. Developing chronic kidney disease (CKD) at the age of ≤ 40, baseline serum creatinine level (SCr) of more than 1.5 mg/dL, and cardiovascular disease increased the risk of ESKD by 4, 1.8, and 2.4 times; respectively. Patient survival analysis revealed a fourfold increase in mortality if the glomerular filtration rate (GFR) declined more than 5 cc/min annually and if CKD was diagnosed at the age of ≤ 40. Vascular thrombotic events or ESKD in the course of disease increased the risk of death by approximately 6- and 7-fold, respectively. Kidney survival was 48% by the age of 60 and 28% by the age of 70. Patient survival was 86.05% at the age of 60 and 67.99% at the age of 70. Additionally, men had a significantly better renal function and survival than women. CONCLUSION: Elevated baseline SCr and cardiovascular disease can increase ESKD risk in ADPKD patients. A rapid decline in GFR, ESKD development, and vascular thrombotic events increase the risk of death, but early CKD can affect both.  DOI: 10.52547/ijkd.7551.

Predictor Factors of Return to Work in Workers with Kidney Transplantation in Iran: A Retrospective Cohort Study.

INTRODUCTION: Return to work after a kidney transplantation in a previously functioning person is determined by a number of medical and non-medical factors. In this regard, this study was to investigate the factors that influence return to work in kidney transplant recipients. METHODS: This retrospective cohort study was conducted in patients with kidney transplant in the main nephrology center in Tehran (December to April 2022). The primary outcome was the cumulative rate of return to work at 3, 6, and 12 months after transplantation. The secondary outcome was to compare the occupational, individual, and disease-related factors between patients who had returned to work and those who had not. RESULTS: Among 214 kidney transplant recipients, the overall cumulative rate of return to work after kidney transplantation at 3, 6 months, and 12 months were 44.4%, 63.1% and 69.6%; respectively. According to the univariate analysis, male sex, age less than 40 years, nonphysical jobs, job satisfaction, employer support, partner support, and absence of diabetes mellitus significantly affected the time of return to work (P < .05). According to the multivariate analysis, absence of diabetes mellitus, nonphysical jobs and job satisfaction had greater impact on the time of return to work (P < .05). CONCLUSION: The results showed that older age, female gender, having a physical job, the presence of diabetes mellitus, lack of job satisfaction, and employer and partner support are associated with not returning to work in these patients and adjusting factors linked to the work environment and support of colleagues and supervisors might play an important role in improving the general condition of these patients.  DOI: 10.52547/ijkd.7210.

A Novel Mutation in CLDN16 Gene Causing Familial Hypomagnesemia, Hypercalciuria, Nephrocalcinosis in An Iranian Family.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder that is characterized by renal magnesium wasting, hypercalciuria and eventually kidney failure which mostly affects children and young aged adults. Mutation of genes of claudin-16 and claudin-19 are involved in the pathogenesis of this disorder, which leads to renal magnesium and calcium wasting. A 35-year-old man with end-stage kidney disease (ESKD) was referred to our clinic due to bilateral nephrocalcinosis, detected by ultrasonographic study, for further evaluation. Detailed investigations revealed that his siblings had also similar presentations of hypomagnesemia, hypercalciuria, nephrocalcinosis and chronic kidney disease (CKD). Sanger sequencing showed a novel mutation (c.338G > A: p.C113Y) at the second exon of the CLDN16 gene. The patient underwent kidney transplantation and his siblings received only medical treatment. In young patients with ESKD and concomitant nephrocalcinosis, especially where there is a family history of CKD/ESKD, genetic evaluation is strongly recommended.  DOI: 10.52547/ijkd.6845.

Crescentic Glomerulonephritis, A Rare Presentation of Alport Syndrome.

Crescentic glomerulonephritis (GN) is a feature of severe glomerular injury. Anti-GBM disease, immune-complex mediated glomerulonephritis, and ANCA-associated vasculitis are the main causes of crescentic GN. Alport syndrome is a progressive form of hereditary nephritis presenting with hematuria and progression to proteinuria and renal failure. Herein we present a 16-year-old male with rapidly progressive glomerulonephritis syndrome, sensory-neural hearing loss, and a family history of hematuria and proteinuria in his mother and aunt. Light microscopic examination shows cellular crescent in glomeruli. In an electron microscopy study, GBM changes compatible with Alport syndrome were identified. Alport syndrome rarely can be presented as crescentic GN. Electron microscopy is necessary for the diagnosis of this type of pauci-immune crescentic glomerulonephritis.

Effects of l-carnitine supplement on serum amyloid A and vascular inflammation markers in hemodialysis patients: a randomized controlled trial.

OBJECTIVE: We studied the effects of l-carnitine supplement on serum amyloid A (SAA), a systemic inflammation marker, and vascular inflammation markers in hemodialysis patients. DESIGN: This was a randomized, double-blind, placebo-controlled trial. SETTING: The study was performed in Soodeh Hemodialysis Center in Islamshahr, Iran. PATIENTS: We included 36 hemodialysis patients (15 men and 21 women). INTERVENTION: The patients on hemodialysis were randomly assigned to either a carnitine or a placebo group. Patients in the carnitine group received 1,000 mg/day oral l-carnitine for 12 weeks, whereas patients in the placebo group received a corresponding placebo during the study. MAIN OUTCOME MEASURES: Serum free carnitine, SAA, soluble intercellular adhesion molecule type 1, soluble intercellular adhesion molecule type 2, soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, and oxidized low-density lipoprotein were measured at baseline and at the end of week 12 of the study. RESULTS: Mean serum free carnitine concentration increased significantly to 150% of baseline in the carnitine group at the end of week 12 (P < .001), whereas serum SAA showed a significant 32% decrease (P < .001). No significant changes were observed in the serum concentrations of free carnitine and SAA in the placebo group during the study. There were no significant differences between the two groups in mean changes in serum soluble intercellular adhesion molecule type 1, soluble intercellular adhesion molecule type 2, soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, and oxidized low-density lipoprotein concentrations. CONCLUSION: The study indicates that l-carnitine supplement reduces serum SAA, which is a risk factor for cardiovascular diseases in hemodialysis patients, but has no effect on vascular inflammation markers.

Effects of L-Carnitine supplement on plasma coagulation and anticoagulation factors in hemodialysis patients.

BACKGROUND: Hypercoagulability is an important risk factor for thrombosis and its complications in hemodialysis patients. This study was designed to investigate the effects of l-carnitine supplement on plasma coagulation and anticoagulation factors in hemodialysis patients. METHODS: Thirty-six hemodialysis patients were randomly assigned to either a carnitine or a placebo group. Patients in the carnitine group received 1000 mg/day oral l-carnitine for 12 weeks, whereas patients in the placebo group received a corresponding placebo. At baseline and the end of week 12, 5 mL blood was collected after a 12- to 14-hour fast and plasma fibrinogen concentration, activity of plasma protein C, coagulation factors V, VII, IX, and serum concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor type-1 (PAI-1), free carnitine, and C-reactive protein (CRP) were measured. RESULTS: In the carnitine group, mean serum free carnitine concentration increased significantly to 150% of baseline (p < 0.001), whereas plasma fibrinogen and serum CRP had 98 mg/dL (p < 0.01) and 41% (p < 0.01) significant decreases, respectively, at the end of week 12 compared with baseline. The reductions were significant compared with the placebo group (p < 0.05). No significant differences were observed between the two groups with regard to mean changes of the activity of plasma protein C, coagulation factors V, VII, IX, and serum PAI-1 to tPA ratio. CONCLUSION: l-Carnitine supplement reduces serum CRP, a marker of systemic inflammation, and plasma fibrinogen, an inflammation-related coagulation factor, in hemodialysis patients. Therefore, l-carnitine may play an effective role in preventing cardiovascular diseases in these patients.

The Added Value of Trabecular Bone Score in Fracture Risk Assessment of Kidney Transplant Recipients.

INTRODUCTION: Trabecular Bone Score (TBS) is an index of bone microarchitecture independent of Bone Mineral Density (BMD). Recently, TBS data has been used to optimize the predictive value of the Fracture Risk Assessment Tool (FRAX). The aim of this study was to evaluate the clinical value of FRAX adjustment with TBS in kidney transplant recipients. METHODS: Seventy post-transplant Iranian kidney recipients were included in this study. After the evaluation of BMD and TBS, the risk of major osteoporotic fracture (MOF) and hip fracture (HF) was assessed once with and once without TBS adjustment. The proportion of patients who needed a therapeutic intervention was compared before and after TBS adjustment. The association between TBS and BMD data was also evaluated. RESULTS: The mean age of the patients was 54 ± 8.8 years (range: 40 to 77). The mean TBS of the patients was 1.30 ± 0.12. In multivariate analysis, the TBS was significantly associated with the age (P < .05) and dialysis period (P < .05). A strong correlation was found between the spine BMD and TBS data (r = 0.612, P < .001). A significant correlation was found between the MOF and HF of the patients before and after adjustment for TBS. The proportion of patients needed a therapeutic intervention significantly increased from 17.1% to 25.7% after TBS adjustment of FRAX. CONCLUSION: Adjustment of FRAX with TBS will reclassify the treatment decision in a considerable number of kidney transplant recipients. This clinical value warrants the adjustment of FRAX data with TBS in future workouts.

Splenic abscess due to fungal infection after kidney transplantation; a case report.

Splenic abscess is one of the rare and potentially life-threatening complications after kidney transplantation. Splenic abscess generally occurs in patients who have immunodeficiency state. It becomes more important with the increased use of immunosuppressed drugs and organ transplantation. The clinical presentation of splenic abscess is insidious, often with constitutional symptoms. Left upper quadrant tenderness is an uncommon sign. Therefore, its diagnosis is difficult and requires a high degree of clinical suspicion. We report a case under renal transplantation with recurrent fungal infection in different organs with two episodes of fungemia who died after splenectomy.

First Report of Familial Juvenile Hyperuricemic Nephropathy (FJHN) in Iran Caused By a Novel De Novo Mutation (E197X) in UMOD.

Uromodulin (UMOD) gene mutation causes autosomal dominant Uromodulin-Associated Kidney Disease (UAKD), which in turn leads to end-stage renal disease. This is the first case report of a family with UAKD caused by a novel de novo mutation (E197X) in the UMOD gene. This case is a 28-year-old man with severely reduced kidney function [1]. No similar case was reported in his family history. This report highlights and reminds the importance of genetic screening in young patients involving kidney dysfunction, as the UAKD and some other kidney genetic diseases may be late-onset.

Disseminated strongyloidiasis in a patient with membranoproliferative glomerulonephritis-case report.

Strongyloides stercoralis (SS) is a unique nematode with an auto infective cycle, so that it completes its life cycle within the human host and can live there for many years. In immunocompromised patients, infection can cause Strongyloides hyperinfection syndrome (S.H.S) that is associated with serious morbidity and mortality. As various infections are one of the leading causes of membranoproliferative glomerulonephritis (MPGN), we should consider subclinical strongyloidiasis as a possible underlying disease, especially in endemic areas. Here we describe a case of strongyloidiasis following immunosuppressive therapy for MPGN, the diagnosis of which was made, only a few hours before death, by stomach biopsy.

A 4-year follow-up of living unrelated donors of kidney allograft in Iran.

INTRODUCTION: Shortage of deceased donor kidneys has resulted in an increased rate of kidney transplantation from living unrelated donors (LURDs). However, there are concerns about short-term and long-term morbidity of the donors. This study reports the clinical and biochemical factors in a follow-up program of Iranian LURDs, one of the largest reported series of kidney donors. MATERIALS AND METHODS: Of 7500 individuals who underwent living donor nephrectomies between 2005 and 2008, a total of 1549 participated in this study. They were followed for 18 to 48 months after the kidney donation. The average time for the first study visit was 316.72 days after donation. RESULTS: The mean age of donors was 30.43 ± 6.16 years old. Men consisted 82.5% of the group. Systolic hypertension was detected in 0.2% and diastolic hypertension in 1% of the LURDs; however, anemia prevalence was as high as 47.2%. Hyperuricemia was found in 21.2% of the LURDs, while proteinuria was seen in 13.7%. Glomerular filtration rate was greater than 90 mL/min in 38.2% of the donors, 60 mL/min to 90 mL/min in 54.5%, and less than 60 mL/min in 7.3%. A GFR less than 45 mL/min was seen in 0.1% of the donors. CONCLUSIONS: Data suggested that the LURDs in Iran have an appropriate health condition comparable to other donors in other parts of the world. Considering the high prevalence of hyperuricemia in our population and its importance as a risk factor for kidney failure, monitoring serum uric acid in follow-up programs is suggested.

Recurrence of primary hyperoxaluria after kidney transplantation.

Primary hyperoxaluria is a genetic disorder in glyoxylate metabolism that leads to systemic overproduction of oxalate. Functional deficiency of alanine-glyoxylate aminotransferase in this disease leads to recurrent nephrolithiasis, nephrocalcinosis, systemic oxalosis, and kidney failure. We present a young woman with end-stage renal disease who received a kidney allograft and experienced early graft failure presumed to be an acute rejection. There was no improvement in kidney function, and she was required hemodialysis. Ultimately, biopsy revealed birefringent calcium oxalate crystals, which raised suspicion of primary hyperoxaluria. Further evaluations including genetic study and metabolic assay confirmed the diagnosis of primary hyperoxaluria type 1. This suggests a screening method for ruling out primary hyperoxaluria in suspected cases, especially before planning for kidney transplantation in patients with end-stage renal disease who have nephrocalcinosis, calcium oxalate calculi, or a family history of primary hyperoxaluria.

Quality of life and life events of living unrelated kidney donors in Iran: a multicenter study.

BACKGROUND: A controlled living unrelated kidney donors (LURDs) transplant program has been started from 1988 in Iran. We surveyed LURDs to investigate the extent to which they experienced stressful life events before donation and their quality of life after donation. METHODS: Five hundred donors were approached. Donors were included in the study provided that donation had taken place at least 3 months before the study. Paykel Life Events Scale and The World Health Organization Quality of Life-Brief version (WHOQOL-Bref) were used in this study. RESULTS: Complete data were available for 424 (84.8%) donors. The mean age was 27.6+/-4.6 years and 84.4% of the participants were men. Ninety-five percent of the respondents reported having experienced at least one stressful life event during the 6 months before kidney donation. The three most frequently experienced life events were the increase in life expenses, low income, and household duties. The most stressful life events were job loss, financial problems, and death of a family member. The participants reported more stressful life events with a mean total stress score (112.6+/-75.0) double than the findings of a previous study in normal population. In all the four domains of WHOQOL-BREF, the participating donors scored lower than previously determined community norms. CONCLUSION: We observed that the quality of life of Iranian LURDs may be low and they may be at risk of experiencing more stressful life events. To be most efficient, the health services should continue after donation and compensate for mental health and psychosocial problems as well.