Uromodulin as a potential candidate marker for predicting the course of chronic kidney disease

Uromodulin is a nephrospecific protein that is most common in normal urine. And although it has been known for more than 70 years, the function of uromodulin remains unclear. Uromodulin is involved in regulating the transport of salts, protects against urinary tract infections, namely, the mucous membrane of the bladder, and prevents the formation of kidney stones, as well as plays a role in kidney damage and innate immunity. Serum uromodulin and uromodulin of urine, daily excretion and excretion of uromodulin per 1 milliliter of creatinine clearance are actively studied. Complete genome studies of the association have established a correlation between uromodulin gene mutations and autosomal dominant tubulointerstitial kidney disease.

Surgical treatment of hydronephrosis in children: a single-centre study

Introduction: Hydronephrosis is one of the most commonly diagnosed urinary tract defects in children. It is characterised by various degrees of dilation of the renal pelvis and calyces with concomitant thinning of the renal parenchyma. The dilation is caused by a ureteropelvic junction defect obstructing the outflow of urine from the kidney. Extreme hydronephrosis can lead to a complete lack of function of the affected kidney. The treatment of hydronephrosis involves restoring normal urine outflow from the kidney and depends on the cause of the condition. The decision to perform surgery depends on the rate of progression of abnormalities observed in the renal parenchyma, among other aspects. Aim of the study: The paper presents the experiences of a single centre in the surgical treatment of hydronephrosis in children aged up to 18 years. Materials and methods: In 2016–2020, 77 children underwent surgery for hydronephrosis at the present authors’ department. In 40% of cases, hydronephrosis was diagnosed on antenatal screening, in 31% it was observed on abdominal ultrasound performed due to abdominal pain, in 17% the condition was detected incidentally when the causes of other diseases were being investigated, in 9% urinary tract infection led to the discovery of hydronephrosis and in 3% of cases abdominal trauma was the reason the patient was examined in the first place. In 58% of the subjects, the cause of hydronephrosis was intramural stenosis of the ureteropelvic junction, in 22% it was the presence of accessory vessels and in 20% various other causes were found. In all patients, Anderson–Hynes ureteropyeloplasty was performed. Results: Surgical outcomes were assessed 12 months after the procedure, and in 97.4% of cases they were considered good. A repeat operation was performed in only 2 cases due to a lack of improvement after the original hydronephrosis surgery. Conclusions: Surgical treatment of hydronephrosis caused by ureteropelvic obstruction is an effective and safe method with a low risk of early and late complications.

Cystinuria in Dogs and Cats: What Do We Know after Almost 200 Years?

The purpose of this review is to summarize current knowledge on canine and feline cystinuria from available scientific reports. Cystinuria is an inherited metabolic defect characterized by abnormal intestinal and renal amino acid transport in which cystine and the dibasic amino acids ornithine, lysine, and arginine are involved (COLA). At a normal urine pH, ornithine, lysine, and arginine are soluble, but cysteine forms a dimer, cystine, which is relatively insoluble, resulting in crystal precipitation. Mutations in genes coding COLA transporter and the mode of inheritance were identified only in some canine breeds. Cystinuric dogs may form uroliths (mostly in lower urinary tract) which are associated with typical clinical symptoms. The prevalence of cystine urolithiasis is much higher in European countries (up to 14% according to the recent reports) when compared to North America (United States and Canada) where it is approximately 1–3%. Cystinuria may be diagnosed by the detection of cystine urolithiasis, cystine crystalluria, assessment of amino aciduria, or using genetic tests. The management of cystinuria is aimed at urolith removal or dissolution which may be reached by dietary changes or medical treatment. In dogs with androgen-dependent cystinuria, castration will help. In cats, cystinuria occurs less frequently in comparison with dogs.

An Unusual Occurrence of Erythrocytosis in a Child with Nephrotic Syndrome and Advanced Chronic Kidney Disease

Background: Anemia is common in patients with nephrotic syndrome (NS) for various reasons. Furthermore, anemia can occur in patients with chronic kidney disease (CKD) predominantly owing to inappropriately low erythropoietin (EPO) production relative to the degree of anemia. However, erythrocytosis is uncommon in patients with NS and advanced CKD who are not treated with exogenous erythropoietin stimulating agents, and when present, will necessitate exploration of the other etiologies. Case summary: Here, we describe an 8-year-old girl with erythrocytosis in association with NS and advanced CKD. The patient was found to have erythrocytosis during the evaluation for hypertensive urgency. She also had nephrotic range proteinuria without edema. Serum hemoglobin and hematocrit were 17 gm/dL and 51%, respectively, despite hydration. Renal function test showed an estimated glomerular filtration rate of 30 mL/min/1.73 m2. There was mild iron deficiency anemia with serum iron saturation of 18%. Serum EPO level was normal. Urine EPO was not measured. Renal biopsy showed evidence of focal segmental glomerulosclerosis. Genetic testing for NS showed mutations in podocyte genes: NUP93, INF2, KANK1, and ACTN4. Gene sequence analysis of genes associated with erythrocytosis showed no variants in any of these genes. She required chronic dialysis ten months later and, subsequently, a renal transplantation 14 months after the initial presentation. Conclusion: Since the serum EPO level was normal, an increased sensitivity to EPO is the most probable mechanism of erythrocytosis. The unusual association of erythrocytosis in patients with NS and advanced CKD needs to be studied further in larger studies.

Diabetes mellitus remission in a cat with hyperadrenocorticism after cabergoline treatment

Case summary A 7-year-old spayed female domestic shorthair cat weighing 5 kg was referred with polyuria, polydipsia, lethargy, abdominal distension and dermatologic abnormalities. Diabetes mellitus was diagnosed and treatment was started with a diet for diabetic cats and insulin glargine (1 IU q12h SC). Hyperadrenocorticism (HAC) was suspected and diagnosed based on clinical signs, increased urinary cortisol:creatinine ratio, lack of suppression on low-dose dexamethasone suppression test and abdominal ultrasonography demonstrating bilateral adrenal enlargement. Oral cabergoline (10 μg/kg every other day) was initiated. After the second administration of cabergoline, the cat suffered from clinical hypoglycemia and no longer required insulin. One month after insulin withdrawal, blood work and urine analysis results showed normoglycemia, a normal serum fructosamine concentration (244 μmol/l) and normal urine analysis without glycosuria. Diabetic remission persisted until its death 7 months later. In addition, cabergoline treatment was associated with improvement in clinical signs such as lethargy, seborrhea, alopecia and abdominal distension. Relevance and novel information To our knowledge, this is the first reported case of the use of cabergoline in a cat with HAC, as well as the first reported case of diabetic remission in a cat with HAC after cabergoline treatment. Cabergoline could be an alternative treatment for diabetic cats with pituitary-dependent HAC. Further work should focus on different protocols with greater number of cases.

Recurrent noncirrhotic hyperammonemia causing acute metabolic encephalopathy in a patient with a continent ileocecal pouch: a case report

Introduction Acute encephalopathy, while a common presentation in the emergency department, is typically caused by a variety of metabolic, vascular, infectious, structural, or psychiatric etiologies. Among metabolic causes, hyperammonemia is relatively common and typically occurs in the setting of cirrhosis or liver dysfunction. However, noncirrhotic hyperammonemia is a rare occurrence and poses unique challenges for clinicians. Case presentation Here we report a rare case of a 50-year-old Caucasian female with history of bladder cancer status post chemotherapy, radical cystectomy, and ileocecal diversion who presented to the emergency department with severe altered mental status, combativeness, and a 3-day history of decreased urine output. Her laboratory tests were notable for hyperammonemia up to 289 μmol/L, hypokalemia, and hyperchloremic nonanion gap metabolic acidosis; her liver function tests were normal. Urine cultures were positive for Enterococcus faecium. Computed tomography imaging showed an intact ileoceal urinary diversion with chronic ileolithiasis. Upon administration of appropriate antibiotics, lactulose, and potassium citrate, she experienced rapid resolution of her encephalopathy and a significant reduction in hyperammonemia. Her hyperchloremic metabolic acidosis persisted, but her hypokalemia had resolved. Conclusion This case is an example of one of the unique consequences of urinary diversions. Urothelial tissue is typically impermeable to urinary solutes. However, when bowel segments are used, abnormal absorption of solutes occurs, including exchange of urinary chloride for serum bicarbonate, leading to a persistent hyperchloremic nonanion gap metabolic acidosis. In addition, overproduction of ammonia from urea-producing organisms can lead to abnormal absorption into the blood and subsequent oversaturation of hepatic metabolic capacity with consequent hyperammonemic encephalopathy. Although this is a rare case, prompt identification and treatment of these metabolic abnormalities is critical to prevent severe central nervous system complications such as altered mental status, coma, and even death in patients with urinary diversions.

Pre-Eclampsia Strikes: Could It Be Related This Gland?

Introduction: Primary hyperparathyroidism (PHPT) is rarely diagnosed in pregnancy and if left untreated has the potential to lead to serious maternal and neonatal complications. We describe a case of PHPT with associated complicated pre-eclampsia. Clinical Case29-year-old primigravida admitted at 33 + 6 weeks with fatigue, 10lbs weight gain and elevated BP. Labs revealed potassium 2.9 (3.5-5.2mmol/L), corrected serum calcium (Ca)11.62 (8.4-10.2mg/dL), ionized calcium 1.69 (1.15-1.33mmol/L), PTH 163.9 (15-65pg/mL) and vitamin D 24.6 (30-100ng/mL). Other labs were normal. Urine studies showed 315mg/24h proteinuria and urine calcium of 129.5 mg/24hrs (100-300mg/24hrs). She was started on magnesium sulphate along with labetalol for BP control, given betamethasone for stimulation of fetal lung maturity as well as potassium repletion. Hypercalcemia (HCa) was initially managed with fluids and Lasix intravenously. At 34 + 2 weeks she developed SOB, orthopnea, headaches with new 9lbs weight gain over 5 days and sustained BP elevation. Urgent C-section was done for pre-eclampsia with severe features. Post-operatively, she suffered from postpartum hemorrhage, managed with transfusion of packed red cells and transient placement of a Bakri balloon. Her HCa worsened with Ca 12.56 and cinacalcet was started after delivery. This coincided with gradual improvement of her BP and Ca to 10.8. She declined additional work-up and was discharged in stable condition. Clinical LessonPHPT often goes undiagnosed in pregnancy, with symptoms of fatigue and constipation mimicking common complaints of pregnancy. Studies have also suggested that up to 25% of patients with PHPT during pregnancy present with hypertension and pre-eclampsia and that there is an association between preeclampsia and the presence of parathyroid adenomas. The pathophysiology is unclear but is thought to be due to endothelial dysfunction triggered by hypercalcemia as well as abnormal placentation. No clear guidelines exist for the management of PHPT during pregnancy, with observation and rehydration being the preferred initial options. The use of cinacalcet as well as curative surgical parathyroidectomy when Ca levels persist >11 in the second trimester have also been described. Our patient presented similarly, with severe pre-eclampsia needing urgent C-section, further complicated by persistent severe HCa. Early diagnosis of PHPT, along with treatment including cinacalcet improved her Ca. It is therefore important that PHPT be considered in patients presenting like ours, progressing to severe pre-eclampsia as early reduction of serum calcium may reduce morbidity and mortality. ReferencesMcCarthy, A., Howarth, S., Khoo, S., Hale, J., Oddy, S., Halsall, D., ... & Samyraju, M. (2019). Management of primary hyperparathyroidism in pregnancy: a case series. Endocrinology, diabetes & metabolism case reports, 2019(1).

Calcitonin Changed During Pregnancy in MEN2A With MTC Patient: A Case Report

Background: The diagnosis of MTC during pregnancy was challenging. No definite calcitonin (Ct) cut-off level during pregnancy was defined. Moreover, cytology analysis accuracy in MTC was lower than other thyroid cancers. Stevenson et al. reported that the plasma Ct levels in pregnant women were much higher than normal women. The change in Ct levels during pregnancy was not well described. In this report, we present a case of a pregnant woman with recurrent MTC. The change in Ct levels during pregnancy, diagnosis methods, and proper management were presented here. Clinical Case: A 31-year Thai woman, gravida 2, para 0 at 17 weeks of pregnancy, previously diagnosed with MTC and treated with total thyroidectomy and neck dissection seven years ago. During antenatal care at 14 weeks of pregnancy, the Ct level was 126 pg/ml (raised from 34 pg/ml seven years ago). The neck’s USG demonstrates vascularized hypoechoic lesion at the right thyroid bed with multiple nodules. The Ct wash-out test from this lesion was 200,000 pg/ml. The cytology study showed several clusters of atypical cells possessing monotonous round eccentric nuclei, and the IHC for Ct was positive. Genetic analysis revealed germline mutation in exon 10 of the RET proto-oncogene (NM_020975.4: c.1858T>G, p.C620G). Finally, MEN 2A with recurrent MTC was diagnoses during pregnancy. The other associate diseases were not found (normal urine metanephrines and plasma calcium levels). The Ct level raised highest to 324 pg/ml at 28 weeks of pregnancy and declined to 236 pg/mL a few days after delivery. Within six weeks, the Ct levels raised again (335 and 362 pg/ml at six weeks and three months after delivery). After giving birth, she underwent neck dissection; The Ct level at one month after surgery was still elevated (85 pg/ml). The CT of the chest, abdomen, and bone scan revealed multiple LN and bone metastasis. She regularly followed up in the oncology clinic and did well until nowadays (two years after delivery). After birth, her son could not pass meconium. Causing underwent exploratory laparotomy with double end ileostomy at day nine of life. The histopathology study from serial bowel biopsy demonstrated aganglionosis of the entire colon, which compatible with Hirschsprung’s disease. Genetic study from colonic tissue and blood confirmed the diagnoses of MEN 2A like his mother. Total thyroidectomy before five years of age and investigate for other associated diseases were planned. Conclusion: The Ct levels were elevated throughout the pregnancy. Transient declined of Ct levels during delivery and raised within six weeks suggest that pregnancy did not affect the Ct levels. In this report, we want to present the change of Ct levels during pregnancy, emphasize the diagnosis of MTC and MEN2A in pregnant women, which may change the patient’s prognosis. Not only in the patients but also in their families. Clinicians should be aware of the management of these patients.

Case Report: Pheochromocytoma in a 59-Year-Old Woman Presenting With Hypotension

Background: Pheochromocytoma patients who present with shock are extremely rare. Here, we report a patient who presented with shock and was diagnosed with pheochromocytoma.Case Summary: A 59-year-old woman with a history of hypertension without any treatment for 5 years presented with chest tightness. Vital signs on arrival indicated blood pressure of 78/50 mmHg. Twelve-lead electrocardiogram indicated ST-segment depression in leads II, III, aVF, and V3–V6 and QT prolongation. Coronary angiogram revealed no evidence of coronary artery disease. Contrast-enhanced computed tomography demonstrated an inhomogeneous right adrenal mass (2.5 × 3.0 cm). Her 24-h urinary norepinephrine and catecholamine levels were elevated. The patient underwent laparoscopic right adrenalectomy. Histopathology confirmed adrenal pheochromocytoma with residual necrosis. The patient was diagnosed with pheochromocytoma. During the 2-year follow-up, the patient was asymptomatic, and her blood pressure remained normal without medication. ECG showed that the ST-segment depression in leads II, III, aVF, and V3–V6 and the QT prolongation had disappeared. The patient showed no signs of recurrence, with normal urine norepinephrine and catecholamine levels.Conclusion: Patients with pheochromocytoma can present with hypotension or even shock. Clinicians should suspect pheochromocytoma when a patient with a history of hypertension has sudden hypotension or even shock.