Cortical Nephrocalcinosis Research Articles

Imaging of primary hyperoxaluria with classical renal and skeletal changes.

Primary hyperoxaluria (PH) is a rare metabolic disorder with autosomal recessive inheritance pattern which is due to deficiency of alanine-glyoxylate aminotransferase enzyme. It causes defective glyoxylate metabolism in liver which in turn leads to excessive oxalate production and deposition. Supersaturation of oxalic acid in urine (>45 mg/day) is known as hyperoxaluria which causes nephrolithiasis, cortical nephrocalcinosis and renal insufficiency. Secondary hyperoxaluria is due to over ingestion of oxalic acids or its precursors or can be due to its reduced excretion. Deposition of these highly insoluble calcium oxalate crystals (serum oxalate >30.0 mmol/L) in extra-renal tissues is known as systemic oxalosis. Here we present a rare case of infantile presentation, where nephrocalcinosis sets in at a very early age without nephrolithiasis, leading to ESRD in very early childhood and extra renal deposition in skeletal system.

Development of Pericardial Calcification with Cortical Nephrocalcinosis in a Preterm Infant: A Case Report

Development of Pericardial Calcification with Cortical Nephrocalcinosis in a Preterm Infant: A Case Report

Bilateral nephrocalcinosis in primary hyperoxaluria type 1.

A 31-year-old male presented with recurrent renal stones from the age of 12 years and renal failure secondary to nephrolithiasis on hemodialysis for the past 6 years. He had been born of a consanguineous union and one out of his five siblings also had a history of renal failure secondary to nephrolithiasis. He had moderate anemia. Abdominal X-ray showed bilateral nephrocalcinosis with multiple stones [Figure 1a, upper panel]. Axial computed tomography scan image showed bilateral cortical nephrocalcinosis, and nephrolithiasis [Figure 1b upper panel]. DNA was extracted from the peripheral blood of the patient using a standard extraction method after obtaining written informed consent. All of the 11 exons and exon-intron boundaries of AGXT gene were amplified by polymerase chain reaction (PCR) as previously described.[1] The PCR products were directly sequenced and compared to the AGXT sequence. Analysis revealed c. 33dupC mutation [Figure 1, lower panel]. Overproduction of oxalate in primary hyperoxaluria type 1 which forms insoluble calcium salts accumulates in organs including kidneys manifest as recurrent nephrolithiasis, nephrocalcinosis, or end-stage renal disease.[2] Nephrocalcinosis is characterized by the presence of calcium deposits in the renal parenchyma and may be associated with conditions such as hyperparathyroidism, medullary sponge kidney, renal papillary necrosis, renal tuberculosis, hyperoxaluria, milk-alkali syndrome, sarcoidosis, immobilization, and other conditions associated with hypercalcemia and hypercalciuria, may cause medullary nephrocalcinosis.[3] Among the 178 mutations described in the AGXT gene, Gly170Arg and c. 33dupC occur across populations at a frequency of 30% and 11%, respectively, while the Ile244Thr mutation is prevalent in North Africa and Spain.[4]

Staging studies for evaluation of squamous cell carcinoma. Staging of left temporal squamous cell carcinoma with PET-CT.

Primary hyperoxaluria is a rare congenital disorder of abnormal glyoxylate metabolism with resultant over-accumulation of oxalate, which then binds with calcium and precipitates in the kidneys, resulting in nephrocalcinosis and nephrourolithiasis. As renal function worsens, patients develop systemic oxalosis with calcium oxalate deposition in the soft tissues, musculoskeletal system, cardiovascular system, central nervous system, and eyes [1–5]. There are three common types of primary hyperoxaluria (types I–III). Type I is the most common and severe and involves a mutation in the alanine glyoxylate aminotransferase (AGT) enzyme causing overproduction of oxalate glyoxylate [1]. Type II results from deficiency of glyoxylate reductase and hydroxypyruvate reductase (GRHPR), which results in overproduction of oxalate and L-glyceric aciduria [1, 5]. Type III results from mutation in 4-hydroxy-2oxoglutarate aldolase (HOGA) and is the least aggressive hyperoxaluria type, with most patients not progressing to end-stage renal disease (ESRD) [1]. Imaging findings in primary hyperoxaluria vary depending on patient age and renal function [2–6]. Prior to renal function impairment, imaging is frequently normal. As renal failure develops, cortical nephrocalcinosis and nephrourolithiasis will be seen (Fig. 1). Calcium oxalate subsequently deposits in soft tissues, tendons, and joint capsules, with joint effusions and nodular-appearing tumoral calcinosis (especially in periarticular regions, which can cause erosive arthropathy) [2–6]. As ESRD develops toward the late stage of the disease, musculoskeletal imaging manifestations typically associated with renal osteodystrophy and secondary hyperparathyroidism will develop, such as osteosclerosis, subperiosteal resorption, Brugger-jersey^ spine, and vascular/soft tissue calcifications (also seen in Fig. 1). Abnormal skeletal maturation and pathologic fractures with delayed healing can also be seen but are similarly nonspecific. Oxalate deposition in the subcutaneous and dermal tissues can cause skin necrosis/ulceration, and oxalate deposition in the myocardium, pericardium, ocular and vascular regions has also been described [4–9]. Skeletal findings more specific to primary hyperoxaluria may include irregular diametaphyseal transverse sclerotic bands and wide metaphyseal zones [5]. Lytic lesions can be seen in primary hyperoxaluria, which histopathologically represent foci of calcium oxalate deposition with a granulomatous foreign body histiocytic reaction, which appear essentially identical to brown tumors on The case presentation can be found at doi: 10.1007/s00256-015-2161-1.

Update in pediatric renal sonography: focus on hyperechoic kidneys

For years, US has been the primary modality for monitoring growth and development of the kidneys before and after birth. Good knowledge of the normal imaging appearances of the kidney is mandatory in order to diagnose renal disease. One of the main objectives of sonography is to detect and evaluate congenital uropathies. The definition of urinary tract dilatation is standardized, and the role of US is essential and clearly defined for this diagnosis. Still, we need long-term follow-up in order to correlate the degree of dilatation and renal function. More recently, thanks to highdefinition transducers, more attention has been given to characterization of nephropathies through more careful analysis of the renal cortex and medulla. Cortico-medullary differentiation (CMD; determined by the different tissue characteristics of the cortex and medulla) is a well-established characteristic of renal sonography in neonates and young children. The CMD can be visualized already around 18–20 weeks’ gestation. In the fetus, the thickness of both cortex and medulla increases progressively throughout pregnancy; yet medullary thickness increases more rapidly than cortical thickness, and therefore the cortico-medullary ratio decreases (from 0.5 around 20 weeks’ to 0.4 around 32 weeks’ gestation). Notably, the overall echogenicity of the fetal renal parenchyma decreases with time. It is hyperechoic relative to the liver or spleen during the second trimester and becomes relatively isoor hypo-echoic after 32 weeks’ gestation. Based on these normal references, it is possible to diagnose various nephropathies prenatally (polycystic kidney diseases, nephrotic syndrome, renal vein thrombosis, etc). After birth, there is a massive fluid overload in the kidneys, and this renders the renal parenchyma relatively hyperechoic. This feature is more marked in prematures, but can be observed in term neonates. As mentioned above, CMD is always visualized. The cortico-medullary ratio should be around 0.38. An abnormal ratio can be observed in various conditions. For instance, in smallfor-dates newborns it is decreased to 0.30, whereas in diseases such as congenital nephrotic syndrome, the pyramids will appear small and irregular and the CMD will be difficult to assess. The sonographic pattern of the CMD has become an essential feature for analysis. The CMD can be increased, absent or reversed, and each pattern will suggest a list of differential diagnoses. Reversed CMD (with hyperechoic medulla) or areas of increased echogenicity in the kidney is referred to as “nephrocalcinosis”, and has been the focus of much research. Medullary nephrocalcinosis is the commonest form; it has been linked to hypercalciuria and metabolic diseases. For some, genetic studies are mandatory in order to distinguish between the diagnostic possibilities. Hyperoxaluria type I, proximal tubular acidosis and Dent syndrome are among other diseases that can be diagnosed by the sonographic patterns. Cortical nephrocalcinosis is less frequent. Distinctive patterns of localized or diffuse areas of calcification may Disclaimer Dr. Fred Avni has no financial interests, investigational or off-label uses to disclose.

Cortical nephrocalcinosis in an infant caused by primary hyperoxaluria type 1

An 8-month-old boy was referred for an upper gastrointestinal study for vomiting. Scout abdominal radiograph shows bilateral cortical nephrocalcinosis (Fig. 1, arrows). US shows hyperechoic cortical rim with acoustic shadowing confirming cortical nephrocalcinosis (Fig. 2, arrows). Laboratory and genetic testing confirmed primary hyperoxaluria type 1 (PH-1). PH-1 is a rare autosomal-recessive disorder resulting from deficiency of the hepatic peroxisomal enzyme alanineglyoxylate aminotransferase, which causes excessive oxalate formation and calcium oxalate deposition in various organs. Kidneys show cortical or medullary nephrocalcinosis and recurrent urolithiasis causing progressive renal failure [1]. Skeletal manifestations of PH-1 sometimes result from oxalate deposition but more commonly result from chronic renal failure, leading to secondary hyperparathyroidism and renal osteodystrophy [2]. Findings include metaphyseal sclerotic lines and bands, lucent bands, cystic changes, permeative lucencies and vertebral diffuse or endplate osteosclerosis (rugger jersey appearance). Flat pelvic bones, carpal and tarsal bones, and patella might show a radiolucent rim.

WT1 mutation and steroid-resistant nephrotic syndrome associated with cortical nephrocalcinosis

When compared to medullary nephrocalcinosis, cortical nephrocalcinosis is a rare and usually secondary to acute cortical necrosis or chronic glomerulonephritis. Here, we report two paediatric cases in which cortical nephrocalcinosis developed during the course of persistent nephrotic syndrome due to focal segmental glomerulosclerosis associated with an intronic mutation in the WT1 gene. The cause of development of cortical nephrocalcinosis was uncertain in both patients. This is the first case report of WT1 mutation-related glomerulopathy associated with cortical nephrocalcinosis, although it is currently unclear if the association is coincidental or causally related.

Cortical Nephrocalcinosis in a Patient With History of Preeclampsia

Cortical Nephrocalcinosis in a Patient With History of Preeclampsia

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Type 1 Primary Hyperoxaluria in Pediatric Patients: Renal Sonographic Patterns

Our aim was to review the sonographic features of type I primary hyperoxaluria in children and to correlate the sonographic patterns with the clinical development of end-stage renal disease (ESRD). We performed a retrospective analysis of the clinical and imaging files of 13 patients with type I primary hyperoxaluria who were treated in one institution and of the sonographic patterns and the clinical follow-up reports. We encountered the following two sonographic patterns: medullary nephrocalcinosis in eight patients and cortical nephrocalcinosis in five patients. The sonographic appearance of cortical nephrocalcinosis is quite specific: a hyperechoic peripheral renal cortex with acoustic shadowing behind it. Medullary nephrocalcinosis is less specific because there are many other causes of hyperechoic pyramids. All patients with medullary nephrocalcinosis developed lithiasis during the course of the disease. All patients with cortical nephrocalcinosis but only two of eight with medullary nephrocalcinosis developed ESRD. Sonography can be used differentiate the two patterns of type 1 primary hyperoxaluria. The cortical nephrocalcinosis type carries a higher risk of developing ESRD.

Renal cortical calcification in syngeneic intact rats and those receiving an infrarenal thoracic aortic graft: possible etiological roles of endothelin, nitrate and minerals, and different preventive effects of long-term oral treatment with magnesium, citrate and alkali-containing preparations.

Renal cortical nephrocalcinosis (C-NC) is a rare disorder of uncertain etiology. Using highly inbred (syngeneic) male Lewis rats, we describe the spontaneous occurrence of histologically detectable C-NC in sham operated control rats (Sham; n=12), its aggravation following grafting of the ascending thoracic aorta from a donor rat to the infrarenal aorta of a recipient (ATx; n=12), and differences in C-NC inhibition after 12 weeks of oral administration of magnesium (Mg), citrate and alkali. C-NC is characterized by Kossa-positive areas located in cells of the proximal tubule close to blood vessels and also, to a lesser extent, within glomeruli. After ATx there was vascular overproduction of endothelin (ET-1) but decreased production of nitrate; in renal cortical tissue there was an excess of calcium over Mg and phosphorus and oxalate over citrate. In plasma there was an increase in calcium and creatinine within the normal range. Calcification of tubular cells was eliminated by a preparation containing potassium, sodium and bases (from citrate degradation and bicarbonate) in addition to Mg. Less effective than the latter was Mg-potassium citrate and least effective, Mg citrate. The former treatment also normalized calcemia and urinary nitrate, but only incompletely suppressed ET-1 and had no significant effect on glomerular calcification or tissue and urinary oxalate. Urinary ET-1 excess appeared directly related to the cortical tissue calcium/Mg ratio, and urinary excretion of Mg, citrate and total protein appeared to be inversely related to the severity of C-NC. It was concluded that (1) the highly inbred rat is prone to precipitation of calcium phosphate in the renal cortex; (2) this type of C-NC occurs in close proximity to and within renal vascular tissue and is associated with an imbalance of vasoconstrictors and vasodilators of endothelial origin; (3) effective inhibition of C-NC can be achieved by an alkalinizing combination of Mg, potassium, sodium and citrate, underscoring its utility in the prophylaxis of pathological calcium phosphate deposition. The significance of these findings for the etiology and treatment of clinical disorders with renal and vascular calcification is uncertain and requires further investigation.

Renal cortical nephrocalcinosis

Renal cortical nephrocalcinosis

Abnormal calcifications in the urinary tract.

A wide variety of calcifications may develop in the urinary tract. Calculi, the most common form of urinary tract calcification, are usually radiopaque due to their calcium content, whereas cystine stones tend to be less opaque. In cortical nephrocalcinosis, calcification may be spotty or may appear as a thin rim outlining the cortex. Intracystic calcification is usually thin and peripheral and is often described as having an "eggshell" appearance. In renal masses, pure central calcification usually indicates malignancy, although malignancy may also be present with pure peripheral calcification. An incomplete ring of calcification seen over the central portion of the kidney should suggest the presence of an abnormal vascular structure. A sloughed papilla may lead to calcification that is usually triangular or ring-shaped or has a broken rim pattern. Ureteral calculi usually have a uniform radiopacity, whereas phleboliths are often less opaque centrally. Like renal calculi, bladder calculi usually contain a calcium component; they may be laminated, faceted, spiculated, or seedlike in appearance. Urachal carcinoma is commonly associated with tumor calcification, which typically occurs at the dome of the bladder. Schistosomiasis of the bladder may produce mural calcification with a typical thin arcuate pattern and may be associated with calcification in other portions of the urinary tract. Although urinary tract calcifications may be difficult to characterize specifically, they can be classified according to location, appearance, and relation to various pathologic conditions.

Renal Cortical Nephrocalcinosis: A Manifestation of Extrapulmonary Pneumocystis carinii Infection in the Acquired Immunodeficiency Syndrome

A 38-year-old man with acquired immunodeficiency syndrome (AIDS) demonstrated atypical nephrocalcinosis on abdominal x-ray. Computed tomography (CT) scanning showed the calcifications to be predominantly in a cortical distribution. The patient had evidence of disseminated Pneumocystis carinii infection, and histologically the renal calcifications occurred in areas of renal Pneumocystis infection. Intrarenal infection with Pneumocystis carinii can be added to the causes of nephrocalcinosis. However, the radiologic picture is so unique that it should suggest the diagnosis in the appropriate patient.

Die Nephrokalzinose im Kindesalter

Ultrasonography is the method of choice for the detection of medullary or cortical nephrocalcinosis in infancy and childhood. Compared with abdominal radiographs and computed tomography even smallest calcifications are detected more accurately. Using furosemide, ACTH, steroids or high doses of vitamin D, early forms of medullary nephrocalcinosis associated with a faint hyperechogenic rim at the margins of the renal pyramids can be diagnosed by ultrasound. Idiopathic hypercalciuria, Bartter's syndrome and renal tubular acidosis cause medullary nephrocalcinosis, whereas cortical nephrocalcinosis is the result of renal vein thrombosis; primary hyperoxaluria is associated with cortico-medullary calcifications. Due to the localisation of the nephrocalcinosis and the age distribution of the diseases, sonography merely enables us to narrow down differential diagnosis.

Inhibition of experimental nephrocalcinosis with a prostaglandin synthetase inhibitor.

Nephrocalcinosis was induced in a group of experimental rats by means of intraperitoneal injections of 10% calcium gluconate. Two further groups of rats were treated with indomethacin and flurbiprofen (Froben) before receiving the i.p. calcium gluconate, to study the effects of prostaglandin inhibition on the process of renal parenchymal calcification. Tissue calcification was studied by means of contact microradiography and histology. Quantitative calcium analysis was by means of energy dispersive analysis of X-rays (EDAX). There was a marked inhibition of cortical nephrocalcinosis and a significantly reduced calcium concentration (P less than 0.005) in the animals treated with a prostaglandin inhibitor compared with the animals given i.p. calcium gluconate alone. This study suggests that prostaglandins are involved in the process of renal parenchymal calcification and may be aetiologically significant in the pathogenesis of stone formation.