Cystinuria is a rare genetic disorder inherited by an autosomal recessive pattern which affects the transmembrane transporter for the base amino acid cystine. It has a general prevalence of 1 in 7000 ...with demographic variations. Patients with cystinuria have excessive urinary excretion of cystine, which can lead to the formation of stones. Up to 70% of patients will develop chronic kidney disease that can progress even to end-stage renal disease. Symptoms usually start in the first two decades of life with a typical presentation consisting of flank pain and renal colic, usually accompanied by urinary tract infection and deterioration of kidney function. Men are typically affected twice as often as women and have a more severe clinical course. Diagnosis is made by spectrophotometric analysis of the stones that are collected after spontaneous expulsion or medical intervention. Genetic testing is not mandatory but is recommended in uncertain cases or as a part of genetic counseling. Treatment consists of diet modification, alkalization of urine, and thiol-based therapies if other measures fail to prevent stone formation. In pregnancy, cystinuria with the formation of cystine stones represents a therapeutic challenge and requires a multidisciplinary approach consisting of an uro-nephrology team and a gynecologist. We present the case of a 34-year-old woman with cystinuria on whom the diagnosis was made by analysis of the expulsed stone. While her previous pregnancies were without complications, her third pregnancy was accompanied by frequent urinary tract infections, acute worsening of kidney function, and urological interventions during pregnancy due to the formation of new stones. Despite the complicated course, the pregnancy was successfully carried to term with the delivery of a healthy female child.
Introduction
Genetic kidney diseases are underdiagnosed; namely, from 7% to 40% of patients suffering from chronic kidney disease (CKD) can carry a pathogenic variant, depending on population ...characteristics. Hereditary tubulointerstitial kidney diseases, including autosomal dominant tubulointerstitial kidney diseases (ADTKD), are even more challenging to diagnose. ADTKD is a rare form of genetic kidney disease resulting from pathogenic variants in the
MUC1, UMOD, HNF1B, REN, SEC61A1,
and
DNAJB11
genes. There is no typical clinical or histopathological sign of ADTKD, it is characterized by progressive CKD, an autosomal dominant inheritance pattern, and tubular atrophy with interstitial fibrosis on kidney biopsy. There is no significant proteinuria, and the urinary sediment is bland. The patients usually do not have severe arterial hypertension. There can be a history of early gout, especially when compared to the UMOD gene variants. Children can have enuresis due to a loss of renal concentration. On ultrasound, the kidneys can appear normal or small in size. Renal cysts are not pathognomonic for any of the named diseases. End-stage renal disease (ESRD) develops at the average age of 45, but this can be very variable. Family history that suggests autosomal dominant inheritance and CKD fulfilling the aforementioned characteristics of tubulointerstitial kidney disease should raise suspicion of ADTKD. In the setting of a negative family history for CKD, clinical suspicion should be raised based on clinical characteristics, including early onset of hyperuricemia or gout and compatible histology on the kidney biopsy. Contrary to the aforementioned characteristics of ADTKD, in the case of HNF1B-related disease, there is a more complex clinical presentation with extrarenal manifestations of the disease (diabetes mellitus, hypomagnesemia, neurologic and psychiatric disturbances, etc.). The diagnosis of ADTKD is based on a positive family history and a detection of the pathogenic variant in one of the genes in an affected individual.
Aim
The aim of our study is to present two case reports of ADTKD with different characteristics (slowly progressive CKD vs. complex clinical presentation with an extrarenal manifestation of the disease) with a literature review.
Methods
A 34-year-old patient with CKD and a positive family history of CKD in whom kidney biopsy showed nonspecific chronic changes, with only genetic analysis confirming the diagnosis of MUC1-related ADTKD. Our second case is of a 17-year-old patient with an unremarkable family history who was initially referred to genetic counseling due to cognitive and motor impairment with long-lasting epilepsy. Extensive workup revealed increased serum creatinine levels with no proteinuria and bland urinary sediment, along with hypomagnesemia. His genetic analysis revealed 17q12 deletion syndrome, causing the loss of one copy of the
HNF1B
gene, the
AATF,
and the
LHX1
gene.
Conclusion
Autosomal dominant tubulointerstitial kidney diseases are challenging to diagnose due to a lack of typical clinical or histopathological signs as well as an uncharacteristic and versatile clinical presentation. Increased clinical awareness is crucial for the detection of these diseases.
Chronic kidney disease (CKD) is a very common chronic non-communicable disease. Phosphate and calcium metabolism disorders are one of the most common features of CKD. Sevelamer carbonate is the most ...widely used non-calcium phosphate binder. Gastrointestinal (GI) injury associated with sevelamer use is a documented adverse effect but is underrecognized as a cause of gastrointestinal symptoms in patients with CKD. We report a case of a 74-year-old woman taking low-dose sevelamer with serious gastrointestinal adverse effects causing colon rupture and severe gastrointestinal bleeding.
Abstract
BACKGROUND AND AIMS
SGLT2 inhibitors have been shown to reduce kidney and cardiovascular events and slowing the decline of renal function in chronic kidney disease. We have examined the ...effect of SGLT2 inhibition in our cohort of ambulatory patients
METHOD
We have included patients with chronic kidney disease, with or without diabetes, fulfilling the criteria for SGLT2 prescription (dapagliflozin and empagliflozin). Eligible patients were started on SGLT2 inhibitors from January to August 2021. Blood pressure, estimated pulse wave velocity, kidney function according to KDIGO; estimated glomerular filtration rate (GFR), chronic kidney disease (CKD) EPI and albuminuria, as well as metabolic profile (lipids, HbA1C, uric acid) measurements were done at the beginning and follow-up. Exclusion criteria were recurrent urinary infection, CKD stage 4 and more, immunosuppressive therapy, diabetes mellitus type 1. Non-parametric statistical tests were used due to sample size, median, 25 and 75 percentile were stated for continuous variables and number and percentage for categorical variables.
RESULTS
A total of 49 patients were enrolled, the average age of 66 years (min-max ranging from 25–75 years), with male predominance (N = 32, 65%). 48% of them completed the follow-up of 4 months (ranging from 3 to 6). A total of 22% had a history of myocardial infarction and/or cerebrovascular incident. Two patients were excluded due to intolerance, one due to non-adherence and one patient was transferred to another hospital. Patients mostly had chronic kidney disease accompanied by diabetes mellitus (DM) type II (N = 31, 63%), 5 (10%) had glomerulonephritis and others (N = 4) had CKD of other origins. There was expected fall in eGFR (median 58 versus median 53 mL/min/1.73m²; P = 0.036) and rise in creatinine values (median 111 versus median 119 umol/L; P = 0.045). No significant change in proteinuria median 0.71 (interquartile range, IQR 0.20–1.23) versus median 0.30 (IQR 0.13–0.59); P = 0.060 nor albuminuria (median 72, IQR 19–720 mg/dU versus median 76 IQR 9–334 mg/dU; P = 0.327) was observed. A total of 35 (92.5%) patients were on RAAS blockade and doses of antihypertensive therapy were not upscaled. There was a statistically significant decline in systolic blood pressure (median 136 versus median 132 mmHg; P = .047) and diastolic blood pressure (median 83 versus median 80.9 mmHg; P = 0.041). There was a significant increase in mean arterial pressure (median 99 versus median 101; P = 0.006) and estimated pulse wave velocity (median 7.65 versus median 8.62; P < .001). There was a trend toward reduction of serum uric acid levels (median 334 mmol/L versus median 265mmol/L; P = 0.182). Glycaemic control was improved with significant change in blood glucose levels (median 6.9 mmol/L versus median 6.1 mmol/L; P = 0.03) as well as Hba1c (median 7.2 versus 6.1, P = 0.013). There were no significant adverse effects in our cohort.
CONCLUSION
SGLT2 inhibitors can be safely used in patients with chronic kidney disease with benefits on blood pressure and metabolic profile which is of utmost importance in this population of very high risk for cardiovascular, as well as, cerebrovascular events. There was a slight decline in kidney function in our cohort which is expected after the initiation of therapy. The effect on estimated pulse wave velocity was not established in our cohort, probably due to the short period of follow-up. Further follow-up of our cohort is needed to establish the lasting effect of SGLT2 inhibitors.
Abstract
Background and Aims
Hepatocyte growth factor (HGF) is a pleiotropic factor derived from mesenchymal cells and is considered a humoral mediator in the interaction of epithelium and ...mesenchyme. The concentration of HGF in the serum is related to blood pressure (BP), but also to serum glucose concentration. Patients with type 1 and 2 diabetes have significantly higher HGF values, especially those with developed atherosclerotic disease and diabetic retinopathy. Moreover, the concentration of serum HGF in patients with diabetes is higher than that in healthy subjects, regardless of their blood pressure (BP) levels. Our aim was to determine the correlation between serum HGF levels and serum glucose levels in subjects with optimal blood pressure and untreated hypertensives.
Method
The subjects were divided into two groups based on the BP values. There were 295 subjects with optimal blood pressure (OBP, BP<120/80 mmHg) and 268 subjects with untreated arterial hypertension (AH, BP>140/90 mmHg). Blood pressure was measured according to ESH/ESC guidelines. Fasting blood samples were drawn, serum glucose and HGF levels were measured using commercial tests.
Results
The average blood pressure was 110/72 mmHg in the OBP group vs 151/92 mmHg in the AH group (p<0,001). Subjects with AH had significantly higher glucose levels than subjects with OBP (4,8±0,5 mmol/l vs. 5,7±1,6 mmol/l, respectively, p<0,001). Serum HGF concentration showed a significant positive correlation to serum glucose levels in the AH group (correlation coefficient = 0,195, p<0,05), but not in the OBP group (correlation coefficient = 0,045, p = 0,06). Serum HGF concentration did not show a significant correlation to blood pressure levels in both groups (all p>0,05).
Conclusion
Serum HGF concentration is associated with glucose levels in subjects with untreated arterial hypertension.
Abstract
Background and Aims
Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder that is characterized by formation of benign tumors of the brain, kidney, eyes, heart, ...lung, liver and skin. The disease is frequently associated with adverse pregnancy outcomes. Our aim is to present two cases of Tuberous sclerosis complex in pregnancy which might be illustrative in the management of these patients.
Method
The first patient was a 32-year-old woman with a history of renal angiomyolipoma (AML) and pulmonic lymphangiomyomathosis (LAM) due to Tuberous sclerosis complex diagnosed at a young age. In the 35th gestational week she had an emergency Cesarean section due to acute retroperitoneal bleeding from angiomyolipoma of the right kidney and gave birth to a preterm male infant (birth mass 2077 g, Apgar 4/6). The patient did not take any medications during the course of pregnancy. Since 2015 she is being treated with everolimus (5 mg/day) due to complications for pulmonic lymphangiomyomathosis, subependymomas and epilepsy and AMLs. After eight years of treatment renal AMLs and LAM and subependymomas show no dynamic in size or number. The second patient was a 29-year-old nulliparous woman who has presented with seizures at the age of 2 and was diagnosed with TSC. At 37th gestational week of a twin pregnancy she gave birth to one male neonate (birth mass 2660 g, Apgar 8/9), while the other fetus died in utero. During the course of the pregnancy she was treated with phenobarbital, folic acid and iron supplementation. Her epilepsy is well-controlled and AMLs show no dynamic in size or number.
Results:
Conclusion
We have showed two cases with relatively good outcomes which have long-term stable disease. Female patients with TSC have increased risk of hemorrhagic complications of AMLs during pregnancy and it can be complicated by intrauterine growth restriction. A multidisciplinary approach is needed in the planning and monitoring pregnancies in these patients to achieve optimal outcomes.
Abstract
Background and Aims
Distal renal tubular acidosis (dRTA) is a rare kidney disease. It can be inherited, i.e. primary (PdRTA), or acquired i.e. secondary (SdRTA). Secondary dRTA is more ...prevalent in the adult population and is usually caused by underlying autoimmune diseases (e.g. Sjogren syndrome). Both forms of dRTA are characterized by alkaline urine, kidney stone formation, nephrocalcinosis, chronic kidney disease, while metabolic acidosis can be variable. The treatment is based on the substitution of alkali substances. Our clinical study aims to describe a cohort of adult dRTA patients (both PdRTA and SdRTA) treated for 18 months by a prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate, in terms of electrolyte disbalance correction, metabolic control, nephrolithiasis complications and kidney function.
Method
Data from seven patients with dRTA (3 with PdRTA and 4 with SdRTA, mean age 44 years, women 71%) taking prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate in our center, were retrospectively collected and analyzed. The patients were previously treated with alkalizing agents (mostly sodium bicarbonate and potassium citrate). Patients were followed up for up to 18 months after inducing prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate was introduced. Kidney function, metabolic acidosis control (serum bicarbonate), serum electrolytes, urinary calcium excretion, and urinary citrate were measured. Nephrolithiasis complications and patient compliance were also evaluated. The urine and blood samples were analyzed two weeks after introducing the new drug and every 3 months afterward. Data are presented as mean ± standard error of the mean. Student T-test was used to calculate p values.
Results
The patients were taking on average 48 mEq of the drug (range 32-72 mEq), the dosage remained the same during the follow-up period (p = 0.365). The average follow-up period was 10 months (range 3-18 months). The metabolic acidosis was well controlled (serum bicarbonate was 24 ± 1.71 mmol/l at baseline, 24.4 ± 1.5 mmol/l at the end of follow-up, p = 0.680). Kidney function remained stable (GFR 73.5 ± 22.67 ml/min/1.73 m2 at baseline, 73 ± 22.69 ml/min/1.73 m2 at the end, p = 0.977). Serum potassium was also well controlled (4.07 ± 0.45 mmol/l at baseline, 4.32 ± 0.40 mmol/l at the end, p = 0.344), as well as calcium in 24-hour urine (2.75 ± 0.59 mmol/24-hour urine at baseline, 2.35 ± 0.12 mmol/24-hour urine at the end, p = 0.222). Urinary citrate levels (calculated as citrate/creatinine ratio) remained in the lower part of the reference range during the follow-up period (103.3 ± 68.3 mmol/mol at baseline, 114.6 ± 64.9 mmol/l at the end, p = 0.775). Two patients had acute renal colic caused by nephrolithiasis, without the need for surgical intervention. Safety and adherence to treatment remained good with no gastrointestinal side effects, one patient discontinued the drug due to headaches.
Conclusion
Our data show that treatment with a prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate in adult dRTA patients can achieve good control of metabolic acidosis and electrolyte disbalance with stable kidney function without the need to escalate the dose of the drug during the follow-up period. The adherence to the treatment remained good with no gastrointestinal side effects.
Abstract
BACKGROUND AND AIMS
Hypercholesterolemia in nephrotic syndrome is commonly resistant to statin therapy and represents an important clinical challenge both for cardiovascular risk prevention ...and to eliminate lipotoxic effect on podocytes. Serum PCSK9 level is elevated in nephrotic syndrome and has a key pathophysiologic role in development and persistance of hyperlipidemia. Thus, we aimed to investigate the role of PCSK9 inhibitors in control of hypercholesterolemia in patients with neprotic syndrome.
METHOD
Consecutive patients with nephrotic syndrome and elevated atherogenic Lp (a) (n = 4) and patients with resistant secondary glomerulonephritis with nephrotic proteinuria (n = 2) were included. In all patients, in addition to full dose statin therapy, evolocumab 420 mg s.c. monthly was introduced. Lipid levels were measured after a median of 4 (range 2–9) months after starting evolocumab.
RESULTS
Nephrotic syndrome was caused by focal segmental glomerulosclerosis in four patients (66.7%) and membranous nepropathy was the cause in two patients (33.3%). Median age of included patients was 49.5 (range 24–70) years. Four patients with primary cause of glomerulonephritis received specific imunosupressive treatment. During follow-up, we observed descrease in glomerular filtration rate (eGFR median 58.5 interquartile range (IQR) 46.7–98.7 mL/min/1.73 m2 versus median 47 IQR 38.25–89.25 mL/min/1.73 m2; P = .046) and persistence of proteinuria median 11 970 IQR (3862–13 765) mg/dU versus median 10 847 (5407–14 340) mg/dU; P = .753. However, despite persistent proteinuria and decrease in eGFR, significant decrease in total cholesterol median 9.10 IQR (6.92–10.87) mmol/L versus median 6.81 (5.4–8.45) mmol/L; P = .028 and LDL cholesterol median 5.40 IQR (4.12–7.25) versus median 4.04 IQR (2.70–4.60); P = .046 was observed. There was no significant difference in Lp (a) and triglyceride levels.
CONCLUSION
PCSK9 inhibitors are a promising new therapeutic option for hyperlipidemia in patients with nephrotic syndrome. Further research, including a larger number of patients, is needed to correctly position PCSK9 inhibitors in treatment of hyperlipidemia in patients with nephrotic syndrome.
Abstract Background Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have ...undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification. Case presentations Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6. Conclusions MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN.
