Risk factors and implications associated with ultrasound-diagnosed nephrocalcinosis in cats with chronic kidney disease.

BACKGROUND: Microscopic nephrocalcinosis is a common pathological feature of chronic kidney disease (CKD) in cats. Detection of macroscopic nephrocalcinosis using ultrasonography and its implications remain unexplored. OBJECTIVES: Identify risk factors associated with ultrasound-diagnosed nephrocalcinosis and evaluate the influence of nephrocalcinosis on CKD progression. ANIMALS: Thirty-six euthyroid client-owned cats with CKD. METHODS: Prospective cohort study. Cats with CKD with and without ionized hypercalcemia were enrolled for renal ultrasonography. Cats were categorized according to the presence or absence of ultrasound-diagnosed nephrocalcinosis. Binary logistic regression was performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression was assessed using linear mixed models. RESULTS: Ultrasound-diagnosed nephrocalcinosis was evident in 61% of CKD cats overall, with increased prevalence (81%) in those with hypercalcemia. At enrollment, higher blood ionized calcium concentration (odds ratio [OR], 1.27 per 0.1 mg/dL; P = .01), plasma phosphate concentration (OR, 1.16 per 0.1 mg/dL; P = .05), plasma creatinine concentration (OR, 1.29 per 0.1 mg/dL; P = .02) and alanine aminotransferase activity (OR, 2.08 per 10 U/L; P = .04) were independent nephrocalcinosis risk factors. The rate of change in log-transformed fibroblast growth factor-23 differed significantly between groups (P = .04). Cats with CKD and nephrocalcinosis had increasing plasma creatinine concentrations (.03 ± .01 mg/dL/month; P = .04) and phosphate concentrations (.06 ± .02 mg/dL/month; P < .001) and decreasing body weight (.02 ± .01 kg/month; P < .001) over time. CONCLUSIONS AND CLINICAL IMPORTANCE: Nephrocalcinosis is prevalent in cats with CKD, especially in those with hypercalcemia. This pathological feature appears to be associated with CKD progression in cats.

A case of diffuse kidney hyperechogenicity in early childhood associated with biallelic PKHD1 variants.

BACKGROUND: Nephrocalcinosis (NC) is characterized by an excessive accumulation of calcium deposits in the kidneys. In children, it is often incidentally discovered with an uncertain prognosis. CASE-DIAGNOSIS/TREATMENT: A 3-month-old girl suspected to have a milk protein allergy underwent an ultrasound that revealed increased echogenicity in the kidney pyramids suggestive of medullary NC. At the age of 18 months, imaging findings revealed not only hyperechogenicity in the medulla but also in the cortex. Over the course of a long follow-up, her kidneys maintained size within the upper limits but showed an increase by age 7. Genetic analysis identified PKHD1 variants, which required structural predictive tools to guide clinical diagnosis. Until the age of 7, her kidney function has remained intact; however, her prognosis is uncertain. CONCLUSIONS: NC in newborns is a rare condition, but its incidence is rising. Recurrent urinary infections or kidney stones may lead to kidney failure. A proactive approach in sporadic NC enables an early diagnosis to orientate clinical supervision and facilitates counseling to support family planning decisions.

Detection of nephrocalcinosis using ultrasonography, micro-computed tomography, and histopathology in cats.

BACKGROUND: Identification of nephrocalcinosis in cats with chronic kidney disease (CKD) is of clinical interest but the ability of ultrasonography to detect nephrocalcinosis is uncertain. OBJECTIVES: To compare ultrasonography, micro-computed tomography (µCT) and histopathology for identification of nephrocalcinosis. ANIMALS: Twelve kidneys from 7 euthyroid client-owned cats with CKD. METHODS: Descriptive study. Renal ultrasonography was performed ante-mortem for nephrocalcinosis detection. Kidneys were grouped based on nephrocalcinosis: present, suspected, or absent. When cats died, necropsy was performed. Renal tissue was evaluated using µCT for macroscopic nephrocalcinosis, and nephrocalcinosis volume-to-kidney tissue ratio (macro-VN:KT) and sagittal nephrocalcinosis area-to-kidney tissue ratio (macro-AN:KT) were calculated. Each kidney subsequently was bisected longitudinally, formalin-fixed, and paraffin-embedded for microscopic nephrocalcinosis assessment using von Kossa and Alizarin red staining with AN:KT (VK-micro-AN:KT and AR-micro-AN:KT) quantified using ImageJ. Data are presented as median (range). Relationships between macroscopic and microscopic AN:KT were assessed using Spearman's correlation. RESULTS: Nephrocalcinosis by ultrasonography was considered to be absent in 3, suspected in 3, and present in 5 kidneys; 1 kidney had nephrolithiasis with nephrocalcinosis. The macro-VN:KT was 0.001%, 0.001%, and 0.019%, and the macro-AN:KT was 0.08%, 0.30%, and 1.47%, respectively. Histologically, VK-micro-AN:KT was 0.21%, 2.85%, and 4.56%, and AR-micro-AN:KT was 1.73%, 5.82%, and 8.90% for kidneys where ultrasonographic macro-nephrocalcinosis was absent, suspected, or present, respectively. A strong correlation was identified between macroscopic (macro-AN:KT) and microscopic (VK-micro-AN:KT) nephrocalcinosis (rs = 0.76; P = .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Ultrasonographically diagnosed nephrocalcinosis correlates well with macroscopic and microscopic nephrocalcinosis at necropsy despite their separation in time.

Nephrolithiasis and/or nephrocalcinosis is significantly related to renal dysfunction in patients with primary Sjögren's syndrome.

OBJECTIVE: The present study compared the clinical features of patients with primary Sjögren's syndrome (pSS) with and without nephrolithiasis and/or nephrocalcinosis to determine factors related to renal dysfunction. METHODS: The clinical features of 68 patients with anti-Sjogren's syndrome antigen A (SSA)/Ro-antibody-positive pSS with and without nephrolithiasis and/or nephrocalcinosis who underwent abdominal computed tomography and/or ultrasonography were retrospectively analysed. RESULTS: Of the 68 patients with anti-SSA-antibody-positive pSS, 23 (33%) had renal nephrolithiasis and/or nephrocalcinosis, whereas 45 (67%) did not. Fourteen (20%) patients had renal dysfunction at diagnostic imaging. Among five patients who underwent renal biopsy, four patients with renal nephrolithiasis and/or nephrocalcinosis were diagnosed with tubulointerstitial nephritis, and one without nephrolithiasis and/or nephrocalcinosis was diagnosed with minimal change nephrotic syndrome. Estimated glomerular filtration rate at diagnostic imaging was significantly lower in patients with than without nephrolithiasis and/or nephrocalcinosis group (P = 0.010). In addition to nephrolithiasis and/or nephrocalcinosis (odds ratio [OR], 3.467; P = 0.045), the gap between serum sodium and chloride concentrations (OR, 10.400; P = 0.012) and increased urinary ß2-microglobulin (OR, 5.444; P = 0.033) were associated with renal dysfunction at the time of diagnostic imaging. CONCLUSION: Nephrolithiasis and/or nephrocalcinosis, normal anion gap metabolic acidosis, and tubulointerstitial damage are associated with renal dysfunction in patients with pSS.

Radiological features of nephrocalcinosis, a common but forgotten entity.

Nephrocalcinosis refers to calcium deposition in the form of calcium oxalate or calcium phosphate in the renal parenchyma and tubules. After diagnosis, the cause of nephrocalcinosis must be established to carry out a comprehensive approach to this entity. Although this is a common finding, it can be underdiagnosed due to the lack of knowledge of the different presentation patterns that exist. Many causes have been described related to this disease.A pictorial review about the most common features of cortical and medullary nephrocalcinosis both in ultrasound and CT is presented in the present work as well as a review of its main causes and graphics to easily recognize each pattern.

Nephrocalcinosis in a Transplanted Kidney: A New Sign of Chronic Tacrolimus Nephrotoxicity.

Calcineurin inhibitors are potent immunosuppressive drugs in solid-organ transplantation and multiple autoimmune diseases. Their use is associated with the acute impairment of glomerular filtration and chronic interstitial fibrosis. The latter is mediated by the accumulation of matrix proteins. In this case report, we present a kidney transplant patient with chronic and progressive allograft failure that was associated with nephrocalcinosis. He did not have hypercalcemic-hypercalciuric states such as hyperparathyroidism, sarcoidosis, and hyper-vitaminosis D; normocalcemic-hypercalciuric states such as distal renal tubular acidosis, medullary sponge kidney, excessive use of high-dose loop diuretics, and beta-thalassemia; hyperphosphaturic conditions; and hyperoxaluria. Moreover, his calcifications were limited to the transplanted kidney and spared the native kidneys and extrarenal tissues, and his renal function had improved and stabilized for 6 months after discontinuation of prolonged-release tacrolimus (Advagraf), indicating a cause and an effect phenomenon. Nephrocalcinosis was suspected after ultrasonography and confirmed by computed tomography scanning. Hence, allograft nephrocalcinosis may indicate chronic tacrolimus nephrotoxicity.

Symptomatic renal papillary varicosities and medullary nephrocalcinosis.

BACKGROUND: Nephrocalcinosis is often asymptomatic but can manifest with renal colic or hematuria. There is no reported association between nephrocalcinosis and renal vascular malformations, which may also be a source of hematuria. We herein present a case of a patient with hematuria related to nephrocalcinosis and renal papillary varicosities. These varicosities were diagnosed and successfully treated with flexible ureteroscopy and laser fulguration. CASE PRESENTATION: A 24-year-old female with a history of epilepsy (on zonisamide), recent uncomplicated pregnancy, and new diagnosis of nephrocalcinosis presented with right flank pain and intermittent gross hematuria. Imaging revealed intermittent right sided hydronephrosis. A cystoscopy identified hematuria from the right ureteral orifice. Diagnostic flexible ureteroscopy revealed numerous intrapapillary renal stones and varicose veins of several renal papillae. A 200 µm holmium laser fiber was used to unroof these stones and fulgurate the varicosities with resolution of her symptoms for several months. She later presented with left-sided symptoms and underwent left ureteroscopy with similar findings and identical successful treatment. CONCLUSION: Unilateral hematuria from discrete vascular lesions of the renal collecting system may be obscured by other benign co-existing conditions, such as nephrocalcinosis and nephrolithiasis. Although a simultaneous presentation is rare, flexible ureteroscopy with laser fulguration offers an ideal diagnostic and therapeutic modality for these concurrent conditions if symptoms arise.

Juvenile dermatomyositis: a case of delayed recognition with unusual complication of nephrocalcinosis.

Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in children and is characterised by the presence of proximal muscle weakness, heliotrope dermatitis, Gottron's papules and occasionally auto antibodies. The disease primarily affects skin and muscles, but can also affect other organs. Renal manifestations though common in autoimmune conditions like lupus are rare in JDM. We describe a child whose presenting complaint was extensive calcinosis cutis. Subtle features of proximal muscle weakness were detected on examination. MRI of thighs and a muscle biopsy confirmed myositis. Nephrocalcinosis was found during routine ultrasound screening. We report the first case of a child presenting with rare association of dermatomyositis, calcinosis cutis and bilateral medullary nephrocalcinosis.

Clinical analysis of 13 children with primary hyperoxaluria type 1.

A retrospective statistical analysis of primary hyperoxaluria type 1 (PH1) in children from June 2016 to May 2019 was carried out to discover its clinical and molecular biological characteristics. Patients were divided into two groups (infant and noninfant) according to clinic type. There were 13 pediatric patients (male:female = 6:7) with PH1 in the cohort from 11 families (four of which were biological siblings from two families), whose median age of symptom onset was 12 months and median confirmed diagnosis age was 14 months. Infant type (6 patients) was the most common type. The infant type mortality rate (100%) was higher than the noninfant (14.3%) (p = 0.029). The incidence of renal failure in infant patients was 67%, while the noninfant was 14.3%. 8 of 10 patients with nephrocalcinosis (NC) (76.92%, 10/13) were diagnosed by radiological imaging examinations, including X-ray (3 patients), CT (4 patients) and MRI (1 patient). NC was an independent risk factor for renal insufficiency [OR 3.33, 95% CI (0.7-1.2)], p < 0.05). Nine types of AGXT gene mutations were found; 1 type, c.190A > T, were first reported here. The most common AGXT gene mutation was c.679_680del, which occurred in exon 6 (5 patients). The infant type is the most common type of pediatric PH, with a relatively higher ratio of renal failure at symptom onset and poor prognosis. NC is an independent risk factor leading to renal failure, and radiological imaging examination is recommended for patients with abnormal ultrasound examination to identify NC. AGXT gene detection is important for the diagnosis and treatment of PH1 in children.

[18F]-sodium fluoride autoradiography imaging of nephrocalcinosis in donor kidneys and explanted kidney allografts.

Nephrocalcinosis is present in up to 43% of kidney allograft biopsies at one-year after transplantation and is associated with inferior graft function and poor graft survival. We studied [18F]-sodium fluoride ([18F]-NaF) imaging of microcalcifications in donor kidneys (n = 7) and explanted kidney allografts (n = 13). Three µm paraffin-embedded serial sections were used for histological evaluation of calcification (Alizarin Red; Von Kossa staining) and ex-vivo [18F]-NaF autoradiography. The images were fused to evaluate if microcalcification areas corresponded with [18F]-NaF uptake areas. Based on histological analyses, tubulointerstitial and glomerular microcalcifications were present in 19/20 and 7/20 samples, respectively. Using autoradiography, [18F]-NaF uptake was found in 19/20 samples, with significantly more tracer activity in kidney allograft compared to deceased donor kidney samples (p = 0.019). Alizarin Red staining of active microcalcifications demonstrated good correlation (Spearman's rho of 0.81, p < 0.001) and Von Kossa staining of consolidated calcifications demonstrated significant but weak correlation (0.62, p = 0.003) with [18F]-NaF activity. This correlation between ex-vivo [18F]-NaF uptake and histology-proven microcalcifications, is the first step towards an imaging method to identify microcalcifications in active nephrocalcinosis. This may lead to better understanding of the etiology of microcalcifications and its impact on kidney transplant function.

Nephrocalcinosis and Renal Dysfunction in Pediatric Intestinal Failure.

BACKGROUND: Outcomes of pediatric intestinal failure (PIF) have improved recently, with other comorbidities, such as increased echogenicity/nephrocalcinosis on ultrasound (US) in long-term survivors now evident. We evaluated the significance of nephrocalcinosis over time in PIF and its impact on renal function. METHODS: Retrospective analysis on a cohort of PIF patients was performed. Presence of nephrocalcinosis and/or increased renal echogenicity (identified on US), estimated glomerular filtration rate (eGFR; ml ·â€Šmin ·â€Š1.73 m2), renal tubular function, PN volume (ml ·â€Škg ·â€Šday) and PN exposure time (hours/day) were reviewed annually over a follow-up period of 2 years. Outcomes in the nephrocalcinosis versus normal US groups were compared. RESULTS: Forty patients (28 boys, median age 2.7 years) were followed for 2 years. Fifteen (38%) had either increased echogenicity or nephrocalcinosis (group 1) at initial US. US were normal in the remaining 25 (62%) on initial assessment (group 2). eGFR did not differ between group 1 and group 2 at baseline (118 vs 133, P = 0.51) and year 2 (130 vs 131, P = 1.00). The percentage of patients with abnormal markers of tubular function was similar in both groups at year 2 (high urine calcium: creatinine 33 versus 30, P = 0.83; high urine calcium: citrate 39 versus 42, P = 0.87; low urine citrate: creatinine 15 versus 17, P = 1.00; high urine oxalate: creatinine 39 versus 25, P = 0.77). CONCLUSIONS: A large proportion of PIF patients with a history of parenteral nutrition (PN) exposure have nephrocalcinosis and/or increased echogenicity on US. Over a 2-year follow-up period, however, these abnormalities had no impact on eGFR or renal tubular function.

Primary Hyperoxaluria-Imaging of Renal Oxalosis.

Primary Hyperoxaluria is a rare autosomal recessive hereditary disorder due to deficient alanine-glyoxylate aminotransferase enzyme with defective glyoxylate metabolism leading to excessive oxalate production and deposition into the tissues (oxalosis). Deposition of excessive calcium oxalates in nephrons leads to crystallization (nephrocalcinosis) which increases risk for end-stage renal disease. We are presenting a case of primary hyperoxaluria type I confirmed with genetic studies.