The impact of metabolic syndrome on chronic kidney disease development. Insights from a big prospective study.

BACKGROUND: Chronic kidney disease (CKD) can progress over time and cause renal replacement therapy. Studies showed the association between metabolic syndrome (MetS) and CKD. Current evidence is from cross-sectional studies. There is a need for the robust data from big prospective cohort studies with long-term follow-up. This study investigated the association between CKD and MetS after 18 years of follow-up. MATERIAL AND METHOD: Among 15,255 participants aged ≥20 years at baseline (1999-2005), after exclusion of CKD, cancer, and use of corticosteroids, 8987 participants entered the study and followed at a three-year cycle up to 2018. All participants were divided into five subgroups: (1) MetS-free, (2) MetS (DM+, HTN-), (3) MetS+ (DM-, HTN+), (4) MetS+ (DM+, HTN+) and (5) MetS+ (DM-, HTN-). RESULT: At baseline, the mean age of the participants was 39.8 ± 13.3 years; 4996 (55.6%) were females. CKD was developed in 2038 (22.7%) subjects during 18 years of follow-up, of whom 1107 had MetS. After adjusting for the confounding variables, MetS (DM+, HTN+) subgroup had the highest risk of CKD (HR = 1.51, 95% CI = 1.32-1.71). MetS subjects with five components had a higher incidence rate of CKD (HR = 1.43, 95% CI = 1.22-1.68). There was no association between high waist circumference (WC) (HR = 1.08, 95% CI = 0.99-1.19) and high-density lipoprotein (HDL) (HR = 1.07, 95% CI = 0.98-1.18) with CKD. CONCLUSION: CKD significantly develops in patients with MetS. Metabolic syndrome was associated with the development of chronic kidney disease incidence. Hypertension, diabetes, and age were strong indicators, while abdominal obesity and reduced HDL were not associated with the incidence of CKD.

Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study.

BACKGROUND: Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. METHODS: Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). RESULTS: A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. CONCLUSIONS: Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.

Association of monocyte/high-density lipoprotein cholesterol ratio and the carotid intima-media thickness in diabetic patients.

OBJECTIVES: The goal of this study was to see whether there was a link between the monocyte/high-density lipoprotein cholesterol ratio (MHR) and carotid intima-media thickness (CIMT) in people with type 2 diabetes. METHODS: Duplex ultrasonography parameters and demographic, physical, and paraclinical assessments were recorded. Using the t-test, the MHR and CIMT were compared between the two groups. Regression models were also constructed. RESULTS: A total of 118 diabetics and 126 non-diabetics were included in the cross-sectional research. According to the stated diabetes duration, the observed age difference of 7 years might be considered. The MHR and CIMT were not substantially different between the two groups. In the DM and non-DM groups, the Spearman correlations between MHR and CIMT were 0.32 and - 0.08, respectively (p-values = 0.001 and 0.379). Thus, regression models (stratified for DM/non-DM and male/female) revealed that the MHR is a significant predictor of CIMT, but only in the case of male DM individuals, when crudely adjusted for confounders. CONCLUSIONS: In diabetes mellitus, the current investigation found a direct link between MHR and CIMT. In addition, in male diabetic subjects, MHR was demonstrated to be a predictor of CIMT.

Capecitabine induced fingerprint changes.

WHAT IS KNOWN AND OBJECTIVE: Fingerprinting is recognized as an easily accessible means of personal identification; however, fingerprints can be damaged after administration of some chemotherapy agents that result in hand and foot syndrome (HFS). Fingerprint loss may also be due to reasons unrelated to HFS. This study evaluated the incidence of fingerprint changes in patients treated with capecitabine-containing chemotherapy regimens and its relations to various grades of HFS. METHODS: Seventy-one patients who received chemotherapy with or without capecitabine as part of their regimen were enrolled in the study. Fingerprints were collected once before the initiation of chemotherapy and once after the third course of chemotherapy. The fingerprints were examined by the Iranian Society of Forensic Physicians, for probable changes in the post-chemotherapy states. RESULTS AND DISCUSSION: Thirty-seven patients were enrolled in the capecitabine group and 34 in a comparison group. Fingerprint changes were observed in 25 (67.6%) of the 37 patients in the capecitabine group and none in the comparison group. There was no correlation between the occurrence or severity of HFS and fingerprint changes (P = 0.880). In capecitabine group, the total dose and course numbers of capecitabine were not significant in patients with and without fingerprint changes. WHAT IS NEW AND CONCLUSION: Based on our findings, we recommend notifying patients who are considered for capecitabine therapy about the risk of fingerprint changes before the initiation of treatment, as this may have legal implications.

Diabetic Kidney Disease Without Albuminuria: A New Entity in Diabetic Nephropathy.

Non-albuminuric diabetic kidney disease (NA-DKD) is characterized by progressive loss of kidney function with an annual loss of estimated glomerular filtration rate (eGFR) more than 3 mL/ min/ 1.73m2 per year. NA-DKD is also associated with the late manifestation of diabetic kidney disease, characterized by reduced eGFR (< 60 mL/min/ 1.73m2), in the absence of albuminuria (urine albumin-to-creatinine ratio [UACR] less than 30 mg/g. The typical glomerular changes seen in diabetic nephropathy are less frequently observed in normoalbuminuric patients, while they predominantly show mesangial expansion and tubulointerstitial and vascular changes. The prevalence of NA-DKD has been increasing during the past decade, with a wide range of prevalence in different studies. It seems that patients with NA-DKD are more likely to be female and have better metabolic profile including a lower Hb A1c, lower triglyceride, lower cholesterol, lower BMI and systolic blood pressure, and lower rate of retinopathy. Compared to patients with albuminuria, those with NA-DKD show a lower risk for progression to end-stage kidney disease (ESKD), or rapid decline in eGFR. They also have increased risks of death and hospitalization for heart failure compared with non-DKD diabetic patients, but a lower risk in comparison with albuminuric DKD, regardless of GFR. There is no effective treatment for this phenotype of the disease, but limited data support the use of SGLT2 inhibitors to slow chronic kidney disease progression along with appropriate metabolic risk factor control. More clinical research and pathologic studies are needed for a better understanding of the phenotype, prevention, and treatment methods of the disease.  DOI: 10.52547/ijkd.7966.

Capacity for the management of kidney failure in the International Society of Nephrology Middle East region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The highest financial and symptom burdens and the lowest health-related quality-of-life scores are seen in people with kidney failure. A total of 11 countries in the International Society of Nephrology (ISN) Middle East region responded to the ISN-Global Kidney Health Atlas. The prevalence of chronic kidney disease (CKD) in the region ranged from 4.9% in Yemen to 12.2% in Lebanon, whereas prevalence of kidney failure treated with dialysis or transplantation ranged from 152 per million population (pmp) in the United Arab Emirates to 869 pmp in Kuwait. Overall, the incidence of kidney transplantation was highest in Saudi Arabia (20.2 pmp) and was lowest in Oman (2.2 pmp). Chronic hemodialysis (HD) and peritoneal dialysis (PD) services were available in all countries, whereas kidney transplantation was available in most countries of the region. Public government funding that makes acute dialysis, chronic HD, chronic PD, and kidney transplantation medications free at the point of delivery was available in 54.5%, 72.7%, 54.5%, and 54.5% of countries, respectively. Conservative kidney management was available in 45% of countries. Only Oman had a CKD registry; 7 countries (64%) had dialysis registries, and 8 (73%) had kidney transplantation registries. The ISN Middle East region has a high burden of kidney disease and multiple challenges to overcome. Prevention and detection of kidney disease can be improved by the design of tailored guidelines, allocation of additional resources, improvement of early detection at all levels of care, and implementation of sustainable health information systems.

Pemphigus vulgaris and focal segmental glomerulosclerosis (FSGS): First reported case and a review of the literature.

Key Clinical Message: There may be a connection between pemphigus vulgaris and nephrotic syndrome, as evidenced by the occurrence of focal segmental glomerulosclerosis in our pemphigus vulgaris patient and reviewing relevant literature. Therefore, if a patient with pemphigus vulgaris presents with bilateral lower extremity edema or proteinuria detected during urinalysis, it could indicate involvement of the kidneys. Abstract: Pemphigus vulgaris is a type of autoimmune blistering disease characterized by the presence of IgG autoantibodies against desmogleins 3 and 1. It is important to evaluate potential autoimmune associations in patients with pemphigus vulgaris so that appropriate laboratory and physical examinations can be performed to monitor for any increased risk of other autoimmune disorders. This case report describes a 55-year-old woman who presented with oral and axillary erosions, which were diagnosed as pemphigus vulgaris based on skin histopathology and immunofluorescence. During follow-up, the patient was found to have proteinuria, which led to referral to a nephrologist. The patient was diagnosed with nephrotic syndrome and minimal change disease after a biopsy. Despite treatment, the patient's proteinuria persisted and serum creatinine levels increased, leading to a second biopsy which confirmed the diagnosis of focal segmental glomerulosclerosis. This study reports on the first case of pemphigus vulgaris with focal segmental glomerulosclerosis and reviews the literature on the co-occurrence of acquired immunobullous diseases and nephrotic syndrome of any kind.

Prevalence of Subclinical Hypothyroidism in Chronic Kidney Disease in a Population-based Study: Tehran Thyroid Study.

BACKGROUND: Chronic kidney disease (CKD) is a rising public health concern that has detrimental effects on cardiovascular health and overall survival. Subclinical hypothyroidism (SCH) has been associated with poor outcomes in the general population. It is thought to be more prevalent in CKD subjects, and their coexistence may contribute to poor outcomes in these patients. We aimed to determine the prevalence of SCH in CKD. METHODS: Using data from the Tehran thyroid study, which is a prospective population-based cohort study, adult subjects with an estimated Glomerular Filtration Rate (eGFR) of 60 mL/min/1.73 m2 or less were selected for studying the prevalence of thyroid abnormalities, as well as other known cardiovascular risk factors. RESULTS: Of 5,626 subjects recruited, 823 (14.6%) individuals had CKD. Individuals with CKD were older, heavier, had a higher prevalence of diabetes, higher serum thyrotropin, and thyroid peroxidase anti-body levels, but lower free thyroxine levels. The prevalence of SCH was 7.3% and 5.2% (P < 0.001) in kidney disease and non-kidney disease subjects, respectively. However, there was no difference in the risk of SCH between CKD and non-CKD subjects after adjustment for age, sex, BMI, smoking, and TPOAb (OR: 1.28; 95%CI, 0.89 - 1.83). None of the metabolic markers compared between the CKD subgroups of those with and without SCH remained statistically significantly different after adjusting for age and gender. CONCLUSIONS: The prevalence of SCH was not higher in CKD after controlling for confounding factors. Besides, CKD subjects with and without SCH had no different metabolic parameters.

Assessment of Serum and Urine Neurophil Gelatinase- Associated Lipocalin (s-NGAL and u-NGAL) Level as a Predictive Factor of Disease Progression in Diabetic Nephropathy in Type 2 DM.

INTRODUCTION: Diabetic nephropathy (DN) is a major complication of diabetes Mellitus. Early detection and intervention of DN can slow its progression and improve patients' outcomes. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of tubular damage might become a useful biomarker for the evaluation of renal involvement in diabetic patients. We aimed to evaluate the serum and urine NGAL(s-NGAL and u-NGAL) in type 2 diabetic patients and its correlation with different stages of diabetic nephropathy. METHODS: This cross-sectional study was designed on 198 subjects consisted of 50 controls and 148 type 2 diabetes patients (50 normoalbuminuric, 58 microalbuminuric, and 40 macroalbuminuric). The study was conducted with measuring s-NGAL and u-NGAL, albumin and spot urine creatinine were also measured. RESULTS: A highly increased level of s-NGAL was detected in macroalbuminuric group compared with controls, normoalbuminurics and microalbuminurics (P < .01). Highly raised u-NGAL levels were observed in macroalbuminurics in comparison with controls (P < .01). ROC curve demonstrated the best sensitivity and specificity of s-NGAL/u-NGAL for the macroalbuminuric state (sensitivity, 26% and 60%; specificity, 98% and 72%; respectively), in which the best cut-off points for the detection of macroalbuminuric state for s-NGAL/u-NGAL were 300 ng/mL and 71.4 ng/mL, respectively. CONCLUSION: Serum and urine-NGAL are elevated in type 2 diabetic patients, with or without albuminuria, s-NGAL level clearly correlates with severity of renal damage caused by DN and u-NGAL increases in macroalbuminuric state. S-NGAL could be a useful, noninvasive, available and practical test for evaluation of diabetic renal involvement. We could suggest u-NGAL as a probable predictor of macroalbuminuria.

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in the Middle East.

Kidney failure is the permanent impairment of kidney function associated with increased morbidity, hospitalization, and requirement for kidney replacement therapy. A total of 11 countries in the Middle East region (84.6%) responded to the survey. The prevalence of chronic kidney disease in the region ranged from 5.2% to 10.6%, whereas prevalence of treated kidney failure ranged from 152 to 826 per million population. Overall, the incidence of kidney transplantation was highest in Iran (30.9 per million population) and lowest in Oman and the United Arab Emirates (2.2 and 3.0 per million population, respectively). Long-term hemodialysis services were available in all countries, long-term peritoneal dialysis services were available in 9 (69.2%) countries, and transplantation services were available in most countries of the region. Public funding covered the costs of nondialysis chronic kidney disease care in two-thirds of countries, and kidney replacement therapy in nearly all countries. More than half of the countries had dialysis registries; however, national noncommunicable disease strategies were lacking in most countries. The Middle East is a region with high burden of kidney disease and needs cost-effective measures through effective health care funding to be available to improve kidney care in the region. Furthermore, well-designed and sustainable health information systems are needed in the region to address current gaps in kidney care in the region.

Pro-Calcitonin, Erythrocyte Sedimentation Rate and C - reactive Protein in Predicting Diabetic Foot Ulcer Characteristics; a Cross Sectional Study.

INTRODUCTION: Considering the importance of early diagnosis of diabetic foot ulcers and its complications, this study aimed to evaluate the accuracy of erythrocyte sedimentation rate (ESR), C - reactive protein (CRP), and pro-calcitonin (PCT) in predicting the ulcer class, osteomyelitis, and peripheral arterial disease (PAD). METHODS: This cross-sectional study was performed on 200 consecutive patients suffering from diabetic foot ulcer who were referred to Infectious Disease Ward. The levels of PCT, ESR, and CRP were measured for all patients and the screening performance characteristics of each marker in predicting the ulcer class, osteomyelitis, and PAD was calculated. RESULTS: The levels of PCT, ESR and CRP were significantly higher in patients with class IV foot ulcer compared to those with class III ulcers (p<0.001). Patients with evidence of osteomyelitis had significantly higher level of PCT, ESR and CRP. The best cutoff points of PCT, ESR and CRP in predicting osteomyelitis were 0.35 ng/ml (86.1% sensitivity, 45.3% specificity), 56.5 mm/hours (95.8% sensitivity, and 50.0% specificity) and 44 mg/ml (90.3% sensitivity, 57.0% specificity), respectively. The presence of PAD was significantly associated with increased levels of the three biomarkers. The best cutoff values for PCT, ESR and CRP in predicting PAD were 0.45 (70.8% sensitivity, 71.7% specificity), 61.5 (83.3% sensitivity, 52.0% specificity) and 49 (83.3% sensitivity, 63.8% specificity), respectively. CONCLUSION: Based on the findings of the present study, although the accuracy of PCT, ESR, and CRP in predicting the severity of diabetic foot ulcers was fair, increase in the three parameters can predict the occurrence of osteomyelitis and PAD following diabetic food development with good accuracy and acceptable sensitivity.

Dabigatran as a Treatment Option for Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a potentially serious adverse drug reaction that can result in lethal vascular thrombosis. Dabigatran is a direct thrombin inhibitor that might be useful in the management of HIT. This study evaluated the efficacy and safety of dabigatran in patients with HIT. We included 43 patients in the study who received dabigatran for the management of suspected HIT, based on 4Ts (thrombocytopenia, timing of platelet count drop, thrombosis or other sequelae, and other causes of thrombocytopenia) scores. Three patients were excluded because they had received dabigatran with a creatinine clearance <15 mL/min. Patients' records were analyzed longitudinally, with 12 months follow-up from the time of initiation of dabigatran, for occurrence of thrombosis, dabigatran-related complications, and outcome. Patients with chronic kidney disease, hepatic impairment, mechanical heart valves, active bleeding, and extremes of weights (<50 and >120 kg) were excluded from the study. Arterial thrombosis was not observed in any of our patients. The platelet counts normalized in all patients except for 2, which was attributed to the underlying comorbidities. We did not observe any hemorrhagic events or significant thrombosis during the follow-up period. Eight patients died from nonthrombotic causes, which were unrelated to adverse effects of dabigatran. Based on our findings, dabigatran could be considered a safe and effective agent in the management of HIT, particularly in the developing countries, where there could be issues with the cost and availability of other agents recommended for this condition. Further studies are needed to validate our findings.

Albumin Utilization Evaluation in a Major Teaching Hospital in Iran: Recommendations for Guideline Development.

OBJECTIVE: Human albumin solution is an expensive colloidal preparation which is commonly used in clinical practice. Due to high cost of albumin, increased rate of the inappropriate use worldwide, and many other reasons, it is imperative to establish a practical protocol to use albumin products and limit its usage. The aim of this study was to identify albumin utilization patterns in a teaching hospital and to demonstrate the importance of the need to reconsider prescribing strategies for albumin administration. METHODS: This retrospective cross-sectional study was performed between August 2016 and December 2016 at Firoozgar Hospital affiliated to Iran University of Medical Sciences, Tehran, Iran. All albumin prescriptions for adult patients during the study period were enrolled for appropriateness evaluation according to the latest evidence-based studies and guidelines. FINDINGS: Among 320 albumin prescriptions, 168 (52.5%) were inappropriate according to the current evidence. The most common irrational causes for the albumin usage were hypoalbuminemia (23.4%), nutritional support (13.7%), neuroprotection in subarachnoid hemorrhage (3%), pretreatment for cancer surgery (2.8%), edema (1.6%), hepatic failure (1.6%), and paracentesis (3%). The total amount of albumin used for 320 patients was 52,050 g, from which 28,470 g was inappropriate resulting in $97,398 wastage. CONCLUSION: These findings, along with aforementioned guidelines, support the requirement for physicians' educational programs and proper strategies for appropriate prescriptions and could also be important in modifying the available guidelines concerning expensive drugs such as albumin.

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.