Cost-benefit analysis of kidney transplant in patients with chronic kidney disease: a case study in Iran.

BACKGROUND: Chronic kidney disease (CKD) is a health problem due to its increasing prevalence and imposes a significant economic burden on the health system. This study aimed to analyze the cost-benefit of kidney transplantation through the valuation of patients with ESRD for a kidney transplant and its costs to help decide this regard. MATERIAL AND METHODS: This study was a descriptive-analytical and cross-sectional economic evaluation study of health interventions performed in Imam Khomeini Hospital in Urmia from the patient's perspective. The records of kidney recipients were used to calculate the direct costs of kidney transplantation based on the government tariff rate in 2021. The willingness to pay for kidney transplantation (benefit) was measured through a questionnaire and with a contingent valuation method from 266 samples of patients with ESRD. The questionnaire designed by the researchers had four scenarios with different chances for kidney transplant success. Validation and test-retest methods were used to check the validity and reliability of the questionnaire. Stata software was used to estimate the regression of the factors affecting the willingness to pay and the kidney transplant demand function. RESULTS: The average cost of a kidney transplant was $877.4. The average willingness to pay for a kidney transplant for four scenarios was estimated at $4733. The mean cost-benefit ratio (BCR) and net present value (NPV) for the four kidney transplant scenarios were 5.39 and $3855. The variables of employment status, awareness of kidney function, number of years with ESRD, insurance coverage, and patients' income significantly affected their willingness to pay. However, the effect of other variables was not significant. The absolute value of price elasticity of kidney transplant demand was also equal to 2.13. CONCLUSION: According to the cost-benefit analysis indexes, the study results showed that a kidney transplant has a net positive benefit for all levels of its probability of success, so the willingness to pay or valuation of patients is about five times the cost of a kidney transplant. Also, the demand for kidney transplantation shows the high sensitivity of the demand for this service to the price. Therefore, preparations for kidney transplantation in patients with ESRD should be considered in situations where the price and cost of transplantation change. The results can help health policy-makers decide to allocate financial resources more efficiently.

Cyclosporine A induces kidney dysfunction by the alteration of molecular mediators involved in slit diaphragm regulation and matrix metalloproteins: the mitigating effect of curcumin.

BACKGROUND: This research aimed at investigating the cyclosporine A intake impact with/without curcumin on podocyte protein gene expressions and matrix metalloproteins (MMPs) changes in rat kidney. METHODS: Thirty-two Wistar male rats were assigned to the control, sham, cyclosporine A, and cyclosporine A with curcumin groups. RESULTS: A significant increase was observed in CD2AP, ACTN4, podocin and also MMP9 and 2, cystatin C levels in the cyclosporine A group following treatment for four weeks, whereas a decrease was found in nephrin gene expression than the control group. In addition, a significant reduction was observed in the cyclosporine A group in glomerular filtration rate (GFR), urine creatinine, and increased plasma creatinine levels than the control group. Using curcumin plus cyclosporine A ameliorated gene expression alterations and increased the reduced amount of GFR, urine urea, and creatinine while reducing the increased plasma cystatine C, urea, and creatinine levels compared with the cyclosporine A group. CONCLUSION: Accordingly, cyclosporine A-induced kidney abnormalities are possibly associated with changes in podocyte intra- and extra-cellular protein gene expression that influence the quality of filtrated fluid via altering the foot process shape and slit diaphragm size. Finally, such impacts are reduced via curcumin as an antioxidant and anti-inflammatory compound.

Identification of Novel Pathogenic PKD2 Variants in Iranian Patients with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a delayed-onset renal disorder that results from a mutation in the PKD1 or PKD2 genes. Autosomal dominant polycystic kidney disease results in end-stage renal disease due to renal cystic dysplasia. The aim of this study was to evaluate, by exon sequencing, the disease-causing variants of PKD2 (exons 4, 6, and 8) in Iranian ADPKD patients. METHODS: Genomic DNA was extracted from 3-5 ml of peripheral blood by the salting-out method. PKD2 exons 4, 6, and 8 were PCR-amplified and sequenced. RESULTS: Three disease-causing PKD2 variants were identified; all three were missense mutations in exon 4. The mutations were AGC → ACC (c.893G>C, cDNA.959G>C, S298T), TAC → TTC (c.1043A>T, cDNA.1109 A>T, Y348F), and GAA → GAT (c.1059A>T, cDNA.1125 A>T, E353D. These novel pathogenic variants may cause loss of the normal protein function. CONCLUSION: Our results suggest that AGC → ACC (c.893G>C, cDNA.959G>C, S298T), TAC → TTC (c.1043A>T, cDNA.1109 A>T, Y348F), and GAA → GAT (c.1059A>T, cDNA.1125 A>T, E353D variants are common in Iranian ADPKD patients. These mutations modify the transmembrane domain and likely influence PC2 function.

Examining the Role of Polymorphisms in Exon 25 of the PKD1 Gene in the Pathogenesis of Autosomal Dominant Polycystic Kidney Disease in ranian Patients.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a highly prevalent life-threatening monogenic disorder with high morbidity and mortality. Roughly 1:400-1000 individuals are affected with this disease worldwide. The development of ADPKD is largely attributed to mutations in the polycystic kidney disease (PKD)1 and PKD2 genes. However, the pathogenicity of the different polymorphisms in PDK1 in the development of ADPKD remains unclear. The aim of this study was to further elucidate the role of the polymorphisms in exon 25 of the PDK1 gene in relation to the pathogenesis of ADPKD in Iranian patients. METHODS: The genomic DNA of 36 Iranian patients with ADPKD was isolated using the standard salting out method. The PCR products were directly sequenced and analyzed. RESULTS: The frequencies of CAG>GAG, ATG>GTG, GTC>GTA, and GTG>ATG polymorphisms in exon 25 of the PKD1 gene were 34 (94.44%), 33 (91.67%), 26 (72.22%), and 5 (13.89%), respectively. The most frequent polymorphism associated with ADPKD was the homozygous CAG→GAG which causes an amino acid change of Q[Gln] to E[Glu] at codon 3005. CONCLUSION: Our data suggests that there is potentially a common polymorphism of PDK1 among the Iranian population with ADPKD. This may aid in the diagnosis and genetic screening of at-risk patients for ADPKD.

A preliminary evaluation of serum level of testosterone, LH, and FSH in patients with varicocele after varicocelectomy as a kidney-related disease.

INTRODUCTION: Varicocele is a common problem with a high prevalence in population with primary and secondary infertilities. The adverse effects of varicocele on spermatogenesis and fertility are known, but the association between clinical varicocele and testosterone is not clear. Hence, we decided to evaluate the serum levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in patients with varicocele after varicocelectomy. METHODS: In this study, 100 patients with varicocele were divided into two groups: hypogonadal patients with testosterone level <280 ng/dL and eugonadal patients with testosterone level >280 ng/dL. The serum levels of testosterone, FSH, and LH were measured before surgery and 3 months after surgery, and the results were analyzed using the SPSS software. P-value <0.05 was considered statistically significant. RESULTS: Patients with varicocele after puberty till 50 years were divided into two groups: hypogonadal (testosterone <280 ng/dL) and eugonadal (testosterone >280 ng/dL) patients who required varicocelectomy. The mean testosterone level before surgery in hypogonadal patients was 215.22±83.31 ng/dL, which reached 326.95±35.125 ng/dL after surgery (P<0.0001), which was significant. There was no significant decrease in the mean FSH level, but there was a significant decrease in the mean LH level after varicocelectomy. In eugonadal group, testosterone level before surgery was 471.90±145.71 ng/dL, which reached 469.57±145.61 ng/dL after surgery, which was not significant. CONCLUSION: In our study, patients who underwent varicocelectomy had improved testosterone levels, so that this increase was more significant in hypogonadal patients than in eugonadal patients. Decrease in LH and FSH levels in all patients was seen after varicocelectomy, which can be due to increase in testosterone levels.

Analysis of Interleukin-17 mRNA Level in the Urinary Cells of Kidney Transplant Recipients with Stable Function.

OBJECTIVES: Kidney transplantation supports patients with end-stage kidney diseases. Many factors control the allograft function in kidney transplant recipients. Interleukin-17 (IL-17) can be used as a non-invasive diagnostic biomarker of rejection. The aim of this study was to evaluate the expression of IL-17 mRNA in urinary cells of kidney transplant recipients with stable function. MATERIAL AND METHODS: A total of 40 renal transplant recipients who were admitted for surgery and 30 healthy controls were enrolled in the study. From each patient, 30 mL urine samples were collected in 50 mL tubes on days 3 and 5 after renal transplantation; also, 30 mL urine samples were obtained from controls. Quantitative Real-Time PCR (qRT-PCR) technique was used for analysis of IL-17 mRNA level in the tested groups; 2-ÄÄCT method was performed for determining the relative gene expression between tested groups. RESULTS: The mRNA expression mean ± SE of fold in patients and controls were 3.58±1.61 fold and 2.85±1.37 fold, respectively. The mRNA expression mean of IL-17 (fold) was not statistically different in tested groups (P-value = 0.63). CONCLUSIONS: In kidney transplant recipients, urinary IL-17 expression provides informative data in relation to the allograft function regardless of allograft pathology.

Prevalence and genotype distribution of cytomegalovirus UL55 sequence in renal transplant recipients in north west of Iran.

Cytomegalovirus (CMV) is one of the most important infections in renal transplant recipients. Kidney transplant is the last hope for the patients with end stage renal diseases. Cytomegalovirus infection can threaten patients and graft survival after transplantation. Four hundred and thirty-four renal transplant recipients contributed to this study. PCR and RFLP analyses were performed in order to determine CMV viremia and its genotypes. CMV viremia was detected in 68 (15.9%) recipients. The mean post-transplantation time in our recipients was 50 months, ranging from 1 to 354 months. Viremia was detected in 31.2%, 30.7%, 17.5%, 10.2%, and 6.4% of the recipients in 0-3, 4-6, 7-12, 13-24, and more than 24 months post-transplantation, respectively. The distribution of gB1, gB2, gB3, and gB4 genotypes was detected as 26.5%, 20.5%, 17.6%, and 5.9%, respectively. Mixed genotype infection was observed in 29.4% of the recipients. Incidence of viremia was higher in the first 6 months after the transplantation compared with the later stages. Moreover, CMV gB1 and mixed genotype infection were more common in our recipients. J. Med. Virol. 88:1622-1627, 2016. © 2016 Wiley Periodicals, Inc.

Outcome of Kidney Transplantation From Living Donors With Multiple Renal Arteries Versus Single Renal Artery.

INTRODUCTION: Receiving a kidney transplant from donors with multiple renal arteries (MRAs) is suggested to be associated with higher risk of vascular and urologic complications and poor allograft outcomes compared to the donors with single renal artery (SRA). We evaluated survival rates in the recipients from donors with MRAs compared to those from donors with SRA. MATERIALS AND METHODS: In a retrospective study on 115 kidney allograft recipients, demographic characteristics and the outcomes of kidney transplantation were compared between the recipients from donors with MRAs compared to those from donors with SRA. These included acute tubular necrosis, acute allograft rejection, hypertension, vascular complications, urologic complications, kidney function indicators, and allograft survival at 1 year. RESULTS: There was no significant difference in the recipients' age, sex distribution, and weight, donors' age, donor-recipient familial relation, urologic complications, and duration of hospitalization between the two groups. However, MRA was significantly associated with a higher likelihood of right-side kidney donation, longer warm and cold ischemia times, and lower glomerular filtration rate and higher serum creatinine concentrations at discharge and 12 months after transplantation, as compared to SRA transplants. No significant difference was seen in late complications including hypertension and renal artery stenosis. One-year graft survival was slightly poorer in the MRA group than the SRA group. CONCLUSIONS: Our results demonstrate that kidney allografts with MRAs are associated with risks but have acceptable outcomes during the 1st year after transplantation, as compared to SRA kidney allografts.

Plasma glutathione peroxidase activity in kidney recipients with and without adverse outcome.

Kidney function is routinely monitored utilizing classic biochemical parameters including serum or plasma creatinine (Cr), and blood urea nitrogen (BUN) concentrations. This study demonstrates that the simultaneous assessment of plasma glutathione peroxidase (pGPx) and Cr levels provides a better strategy for the immediate follow-up of kidney function in organ recipients. Kidney recipients (Krs; n = 22) were recruited. Blood sampling schedule commenced at day 1 (pre-transplantation) and post-transplantation days (i.e., everyday from 1 until day 14, and thereafter on days 21, 28, 35, 42, 49, and 56). pGPx was measured spectrophotometrically. Candidates for transplantation exhibited lower pGPx than control subjects (42 ± 24 vs. 143 ± 31 U/L; p < 0.005). In Krs with a stable post-transplant outcome, pGPx increased to a maximum at day 28 (214 ± 61 U/L). In a Kr diagnosed with acute tubulonecrosis, pGPx provided a better predictive value (threefold increase) than Cr. In a Kr diagnosed with acute rejection, the increment in Cr values was found to be more pronounced than in pGPx values. The pGPx test is simple, inexpensive and automatable, and should be a valuable diagnostic tool of kidney function in organ recipients with and without troublesome outcome for the follow-up during hospitalization period.

Seroprevalence of herpes simplex virus-2 in kidney transplant recipients: a single-center experience.

INTRODUCTION: Viral infections are a real threat in kidney transplant recipients because of their immunocompromised condition. This study aimed to evaluate herpes simplex virus-2 (HSV-2) seropositivity among kidney transplant recipients. MATERIALS AND METHODS: Serum samples of 91 kidney transplant recipients from Urmia, Iran, were examined serologically for antibodies against HSV-2 using an enzyme-linked immunosorbent assay. RESULTS: The mean time from transplantation at HSV-2 testing was 5.04 +/- 4.45 years. The anti-HSV-2 immunoglobulin G antibody was positive in 5.4% of the kidney transplant recipients. Seropositive patients did not present any clinical manifestations of genital herpes infection. There was no association between HSV-2 seropositivity and age, gender, history of hemodialysis and transplantation, blood transfusion, or immunosuppressive regimen. CONCLUSIONS: Seroprevalence of HSV-2 is not high among our kidney transplant recipients. However, it remains a source of concern, considering the compromised immune system in this specific population.

The effect of garlic on cyclosporine-A-induced hyperlipidemia in male rats.

INTRODUCTION: Cyclosporin A (CsA) is a potent immunosuppressive drug. However, it has adverse effects that include elevation of plasma low-density lipoprotein (LDL). This study was designed to determine the effect of garlic on CsA-induced hyperlipidemia in male rats. MATERIALS AND METHODS: Baseline serum blood samples from forty 10-month-old, male Wistar rats were obtained. They received intraperitoneal (IP) injection of CsA (25 mg/kg) for 28 days. Blood samples were again obtained after the 28-day treatment. Sixteen of 40 rats showed increased serum LDL levels. These 16 were divided into 2 groups of 8 rats each. In the first (experimental) group, 8 rats received garlic (tablets, 400 mg/d), CsA (25 mg/kg IP), and regular diet for 28 days. In the second (control) group, 8 rats received the same regimen without the garlic tablets. At the end of the experiment, blood samples were taken from animals in both groups, and LDL levels were assessed. RESULTS: The mean baseline LDL level in animals in the control group was 17.75 +/- 4.1 mg/dL. This increased to 21.5 +/- 1.6 mg/dL after 28 days of CsA administration. After 28 more days, the mean LDL level increased to 25.4 +/- 4.9 mg/dL (P = .004). In animals in the experimental group, the baseline LDL level was 23.8 +/- 3.7 mg/dL, which increased to 31.3 +/- 1.6 mg/dL after the first 28 days (P < .001). After the second 28 days, it decreased to 26.0 +/- 4.8 mg/dL (P = .06), and among 4 animals, the LDL level decreased more than 49%. CONCLUSION: In a Wistar rat model, animals given cyclosporin A subsequently treated with garlic demonstrated reduced LDL levels compared with controls. This treatment may be useful in patients receiving organ transplantations.