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Medullary sponge kidney (MSK) is a description of radiographic features. However, the pathogenesis of MSK remains unclear. MSK is supposed to be the cause of secondary distal renal tubular acidosis (dRTA), although there are case reports suggesting that MSK is a complication of primary dRTA. In addition to these reports, we report 3 patients with metabolic acidosis and MSK, in whom primary dRTA is confirmed by molecular genetic analyses of SLC4A1 and ATP6V1B1 genes. With a comprehensive genetics-first approach using the 100,000 Genomes Rare Diseases Project dataset, the association between MSK and primary dRTA is examined. We showed that many patients with MSK phenotypes are genetically tested with a gene panel which does not contain dRTA-associated genes, revealing opportunities for missed genetic diagnosis. Our cases highlight that the radiological description of MSK is not a straightforward disease or clinical phenotype. Therefore, when an MSK appearance is noted, a broader set of causes should be considered including genetic causes of primary dRTA as the underlying reason for medullary imaging abnormalities., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: To establish better diagnosis thinking and provide advanced understanding of MSK, the CT imaging features, clinical characteristics, and the expression of suspected genes in the kidney spatiotemporal immune zonation and fetal renal development were investigated., Methods: 17 patients with MSK hospitalized in our hospital were selected as our research subjects. Human Phenotype Ontology, MalaCards: The Human Disease Database, GeneCards: The Human Gene Database, Human Protein Atlas, and Single Cell Expression Atlas were used to analyze this disease., Results: In our 17 patients, the incidence of MSK tended to be the same in male and female, and the onset age of MSK was probably 31-50 years old. The top one related disease of MSK was nephrocalcinosis and the most frequent phenotype related to MSK was nephrolithiasis. In addition, the expression of HNF1B, CLCN5, GDNF, ATP6V0A4, ATP6V1B1, LAMA2, RET, ACAN, and ABCC8 has been implicated in both human kidney immune zonation and fetal kidney development., Conclusions: HNF1B, CLCN5, GDNF, ATP6V0A4, ATP6V1B1, LAMA2, RET, ACAN, and ABCC8 could be independent indicators for the diagnosis and preventive intervention of MSK patients, and abnormal kidney development due to mutations in key genes was the underlying cause of MSK., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Ming Li et al.)

Background and Objectives: Microvesicles and exosomes are involved in the pathogenesis of autosomal dominant polycystic kidney disease. However, it is unclear whether they also contribute to medullary sponge kidney, a sporadic kidney malformation featuring cysts, nephrocalcinosis, and recurrent kidney stones. We addressed this knowledge gap by comparative proteomic analysis., Design, Setting, Participants, & Measurements: The protein content of microvesicles and exosomes isolated from the urine of 15 patients with medullary sponge kidney and 15 patients with autosomal dominant polycystic kidney disease was determined by mass spectrometry followed by weighted gene coexpression network analysis, support vector machine learning, and partial least squares discriminant analysis to compare the profiles and select the most discriminative proteins. The proteomic data were verified by ELISA., Results: A total of 2950 proteins were isolated from microvesicles and exosomes, including 1579 (54%) identified in all samples but only 178 (6%) and 88 (3%) specific for medullary sponge kidney microvesicles and exosomes, and 183 (6%) and 98 (3%) specific for autosomal dominant polycystic kidney disease microvesicles and exosomes, respectively. The weighted gene coexpression network analysis revealed ten modules comprising proteins with similar expression profiles. Support vector machine learning and partial least squares discriminant analysis identified 34 proteins that were highly discriminative between the diseases. Among these, CD133 was upregulated in exosomes from autosomal dominant polycystic kidney disease and validated by ELISA., Conclusions: Our data indicate a different proteomic profile of urinary microvesicles and exosomes in patients with medullary sponge kidney compared with patients with autosomal dominant polycystic kidney disease. The urine proteomic profile of patients with autosomal dominant polycystic kidney disease was enriched of proteins involved in cell proliferation and matrix remodeling. Instead, proteins identified in patients with medullary sponge kidney were associated with parenchymal calcium deposition/nephrolithiasis and systemic metabolic derangements associated with stones formation and bone mineralization defects., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_04_24_CJASNPodcast_19_06_.mp3., (Copyright © 2019 by the American Society of Nephrology.)

Heterozygosity for human polycystic kidney and hepatic disease 1 ( PKHD1) mutations was recently associated with cystic liver disease and radiographic findings resembling medullary sponge kidney (MSK). However, the relevance of these associations has been tempered by a lack of cystic liver or renal disease in heterozygous mice carrying Pkhd1 gene trap or exon deletions. To determine whether heterozygosity for a smaller Pkhd1 defect can trigger cystic renal disease in mice, we generated and characterized mice with the predicted truncating Pkhd1 C642* mutation in a region corresponding to the middle of exon 20 cluster of five truncating human mutations (between PKHD1 G617fs and PKHD1 G644* ). Mouse heterozygotes or homozygotes for the Pkhd1 C642* mutation did not have noticeable liver or renal abnormalities on magnetic resonance images during their first weeks of life. However, when aged to ~1.5 yr, the Pkhd1 C642* heterozygotes developed prominent cystic liver changes; tissue analyses revealed biliary cysts and increased number of bile ducts without signs of congenital hepatic fibrosis-like portal field inflammation and fibrosis that was seen in Pkhd1 C642* homozygotes. Interestingly, aged female Pkhd1 C642* heterozygotes, as well as homozygotes, developed radiographic changes resembling MSK. However, these changes correspond to proximal tubule ectasia, not an MSK-associated collecting duct ectasia. In summary, by demonstrating that cystic liver and kidney abnormalities are triggered by heterozygosity for the Pkhd1 C642* mutation, we provide important validation for relevant human association studies. Together, these investigations indicate that PKHD1 mutation heterozygosity (predicted frequency 1 in 70 individuals) is an important underlying cause of cystic liver disorders and MSK-like manifestations in a human population.

In the last decades, proteomics has been largely applied to the Nephrology field, with the double aim to (1) elucidate the biological processes underlying renal diseases; (2) identify disease-specific biomarkers, predictor factors of therapeutic efficacy and prognostic factors of disease progression. Kidney stone disease, and in particular, inherited nephrolithiasis (INL) are not an exception. Given the multifactorial origin of these disorders, the combination of genomics and proteomics studies may complement each other, with the final objective to give a global and comprehensive mechanistic view. In this review, we summarize the results of recent proteomic studies which have expanded our knowledge about INL, focusing the attention on monogenic forms of nephrolithiasis (cystinuria, Dent's disease, Bartter syndrome, distal renal tubular acidosis and primary hyperoxaluria), on polygenic hypercalciuria and on medullary sponge kidney disease.

Background: Medullary sponge kidney is a rare renal malformation, which usually manifests as nephrocalcinosis, renal tubular acidosis, and recurrent urinary tract infections. Medullary sponge kidney is often associated with renal developmental anomalies and tumors, and its exact pathogenesis is not yet clearly explained. Given the key role of the interaction of glial cell line-derived neurotrophic factor gene, GDNF, and the "rearranged during transfection" proto-oncogene, RET, in kidney and urinary tract development, variations in these genes are proposed to be candidates for medullary sponge kidney. Hyperparathyroidism is observed in a few patients with medullary sponge kidney, but the exact pathogenesis of this association is unknown. This case report highlights the coexistence of these two conditions associated with RET polymorphism, which contributes toward the understanding of the pathogenesis of medullary sponge kidney., Case Presentation: A 52-year-old Chinese woman with recurrent renal stones presented to our hospital. Subsequently she was diagnosed as having medullary sponge kidney and tertiary hyperparathyroidism and underwent parathyroidectomy. Genomic DNA was isolated from lymphocytes and the GDNF and RET genes were determined by Sanger sequencing. Two RET polymorphisms were found in our patient, one was nonsynonymous c.2071G>A (G691S; rs1799939) located in exon 11, the other was synonymous c.2712C>G. (p.S904S; rs1800863) located in exon 15., Conclusions: We demonstrated a case of medullary sponge kidney combined with tertiary hyperparathyroidism, which contributes to further understanding of the pathogenesis of this disease. Besides, we also found RET G691S/S904S polymorphism in this patient, but additional studies are required to explore the role of the RET gene in medullary sponge kidney with hyperparathyroidism.

Medullary sponge kidney (MSK) is a congenital renal disorder. Its association with several developmental abnormalities in other organs hints at the likelihood of some shared step(s) in the embryogenesis of the kidney and other organs. It has been suggested that the REarranged during Transfection (RET) proto-oncogene and the Glial cell line-Derived Neurotrophic Factor (GDNF) gene are defective in patients with MSK, and both RET and GDNF are known to have a role in the development of the central nervous system, heart, and craniofacial skeleton. Among a cohort of 143 MSK patients being followed up for nephrolithiasis and chronic kidney disease at our institution, we found six with one or more associated non-renal anomalies: one patient probably has congenital hemihyperplasia and hypertrophic cardiomyopathy with adipose metaplasia and mitral valve prolapse; one has Marfan syndrome; and the other four have novel associations between MSK and nerve and skeleton abnormalities described here for the first time. The discovery of disorders involving the central nervous system, cardiovascular system and craniofacial skeleton in MSK patients supports the hypothesis of a genetic alteration on the RET-GDNF axis having a pivotal role in the pathogenesis of MSK, in a subset of patients at least. MSK seems more and more to be a systemic disease, and the identification of extrarenal developmental defects could be important in arousing the suspicion of MSK in recurrent stone formers.

Medullary nephrocalcinosis is a hallmark of medullary sponge kidney (MSK). We had the opportunity to study a spontaneous calcification process in vitro by utilizing the renal cells of a patient with MSK who was heterozygous for the c.-27 + 18G>A variant in the GDNF gene encoding glial cell-derived neurotrophic factor. The cells were obtained by collagenase digestion of papillary tissues from the MSK patient and from two patients who had no MSK or nephrocalcinosis. These cells were typed by immunocytochemistry, and the presence of mineral deposits was studied using von Kossa staining, scanning electron microscopy analysis and an ALP assay. Osteoblastic lineage markers were studied using immunocytochemistry and RT-PCR. Staminality markers were also analysed using flow cytometry, magnetic cell separation technology, immunocytochemistry and RT-PCR. Starting from p2, MSK and control cells formed nodules with a behaviour similar to that of calcifying pericytes; however, Ca₂PO₄ was only found in the MSK cultures. The MSK cells had morphologies and immunophenotypes resembling those of pericytes or stromal stem cells and were positive for vimentin, ZO1, αSMA and CD146. In addition, the MSK cells expressed osteocalcin and osteonectin, indicating an osteoblast-like phenotype. In contrast to the control cells, GDNF was down-regulated in the MSK cells. Stable GDNF knockdown was established in the HK2 cell line and was found to promote Ca₂PO₄ deposition when the cells were incubated with calcifying medium by regulating the osteonectin/osteopontin ratio in favour of osteonectin. Our data indicate that the human papilla may be a perivascular niche in which pericyte/stromal-like cells can undergo osteogenic differentiation under particular conditions and suggest that GDNF down-regulation may have influenced the observed phenomenon., (© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Genetic disorders of the kidney include cystic diseases, metabolic diseases and immune glomerulonephritis. Cystic diseases include autosomal dominant and recessive polycystic kidney disease (ADPKD, ARPKD, respectively). Neonates with enlarged, cystic kidneys should be evaluated for PKD. Patients with ADPKD have cysts and renal enlargement. Most patients present with hypertension, hematuria or flank pain; the most common extrarenal manifestation is polycystic liver disease. Oligohydramnios, bilaterally enlarged kidneys and decreased urine are featured in utero in ARPKD. Medullary sponge kidney is uncommon and features nephrocalcinosis, recurrent calcium stones and a history of polyuria/nocturia and/or urinary tract infections. Alport syndrome (AS) is an inherited disease of the glomerular basement membrane that is usually inherited as an X-linked dominant trait. Most patients with AS present in the first two decades of life with persistent microscopic or gross hematuria. Later, proteinuria is seen and its presence portends disease progression. Other findings may include sensorineural hearing loss and ocular abnormalities. There are various inherited tubulopathies, including Bartter syndrome, a group of renal tubular disorders that consist of two phenotypes with four genotypes. Patients usually present early in life with salt wasting, hypokalemia and metabolic alkalosis. Other features, depending on genotype, may include polyhydramnios and premature birth. Gitelman syndrome is also a salt-losing tubulopathy characterized by hypokalemic alkalosis. The majority of patients with Gitelman syndrome present during adolescence or early adulthood.

Purpose of Review: After it was first described in 1939, medullary sponge kidney (MSK) received relatively little attention. This was because it was believed to have a low prevalence and because it was considered a benign condition. Studies in recent years have been changing these convictions however, hence the present review., Recent Findings: Insight has been obtained on the genetic basis of this disease, supporting the hypothesis that MSK is due to a disruption at the 'ureteric bud-metanephric mesenchyme' interface. This explains why so many tubular defects coexist in this disease, and particularly a distal tubular acidification defect of which the highly prevalent metabolic bone disease is one very important consequence. In addition to the typical clinical phenotype of recurrent stone disease, other clinical profiles have now been recognized, that is, an indolent, almost asymptomatic MSK, and a rare form characterized by intractable, excruciating pain., Summary: Findings suggest the need for a more comprehensive clinical characterization of MSK patients. The genetic grounds for the condition warrant further investigation, and reliable methods are needed to diagnose MSK.

Medullary sponge kidney (MSK) is associated with recurrent calcium stones. Gambaro's group evaluated the relatives of probands with MSK. When prior imaging was not available, they performed renal ultrasounds. They demonstrated familial clustering, providing the best evidence yet that MSK is a heritable disorder. Although a small proportion of MSK cases are associated with variants of glial cell-derived neurotrophic factor (GDNF), the genetic basis for most instances of MSK is not known.

Medullary sponge kidney (MSK) is a renal malformation typically associated with nephrocalcinosis and recurrent calcium nephrolithiasis. Approximately 12% of recurrent stone formers have MSK, which is generally considered a sporadic disorder. Since its discovery, three pedigrees have been described in which an apparently autosomal dominant inheritance was suggested. Here, family members of 50 patients with MSK were systematically investigated by means of interviews, renal imaging, and biochemical studies in an effort to establish whether MSK is an inheritable disorder. Twenty-seven MSK probands had 59 first- and second-degree relatives of both genders with MSK in all generations. There were progressively lower mean levels of serum calcium, urinary sodium, pH, and volume, combined with higher serum phosphate and potassium from probands to relatives with bilateral, to those with unilateral, and to those unaffected by MSK. This suggests that most affected relatives have a milder form of MSK than the probands, which would explain why they had not been so diagnosed. Thus, our study provides strong evidence that familial clustering of MSK is common, and has an autosomal dominant inheritance, a reduced penetrance, and variable expressivity.

Renal cystic diseases in adults are a heterogeneous group of disorders characterized by the presence of multiple cysts in the kidneys. These diseases may be categorized as hereditary, acquired, or developmental on the basis of their pathogenesis. Hereditary conditions include autosomal dominant polycystic kidney disease, medullary cystic kidney disease, von Hippel-Lindau disease, and tuberous sclerosis. Acquired conditions include cystic kidney disease, which develops in patients with end-stage renal disease. Developmental cystic diseases of the adult kidney include localized renal cystic disease, multicystic dysplastic kidney, and medullary sponge kidney. In recent years, many molecular and cellular mechanisms involved in the pathogenesis of renal cystic diseases have been identified. Hereditary renal cystic diseases are characterized by genetic mutations that lead to defects in the structure and function of the primary cilia of renal tubular epithelial cells, abnormal proliferation of tubular epithelium, and increased fluid secretion, all of which ultimately result in the development of renal cysts. A better understanding of these pathophysiologic mechanisms is now providing the basis for the development of more targeted therapeutic drugs for some of these disorders. Cross-sectional imaging provides useful information for diagnosis, surveillance, prognostication, and evaluation of treatment response in renal cystic diseases., (© RSNA, 2010.)

Background and Objectives: Medullary sponge kidney (MSK) is a rare nephropathy characterized by cystic anomalies of precalyceal ducts, nephrocalcinosis, renal stones, and tubule dysfunctions. Its association with various malformations and cases of familial aggregation supports the conviction that genetic factors are involved, but no genetic studies have been conducted to date. It is hypothesized that MSK is due to a disruption at the "ureteric bud/metanephric blastema" interface caused by critical developmental genes functioning abnormally., Design, Setting, Participants, & Measurements: Fifty-five apparently sporadic MSK patients were analyzed by direct DNA sequencing of all exons and exon-intron boundaries of glial cell-derived neurotrophic factor (GDNF) gene and rearranged during transfection (RET) gene, which have a leading role in renal development., Results: Two novel variants were found in heterozygosity in the MSK case population: GDNF{ENST00000344622}:c.-45G>C and c.-27+18G>A in a putative binding domain for paired-box 2 transcription factor. As a whole, eight patients showed these variations: four patients carried the c.[-45G>C; -27+18G>A] complex allele, and the others had the c.-27+18G>A alone. A case-control study revealed that these two alleles were significantly associated with MSK. Five of the eight cases were found to be familial, and the allele variants cosegregated with the disease in a seemingly dominant pattern of inheritance. Patients revealed no mutations in the RET gene., Conclusions: This is the first report identifying GDNF gene sequence variations in patients with MSK and suggesting a role for this gene in the pathogenesis of some cases of the disease.

Background: Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or dilation of precalyceal collecting tubules. Although its pathogenesis is unknown, the association with various congenital diseases suggests that it could be a developmental disorder. In addition to the typical clinical features of nephrocalcinosis and urolithiasis, patients with MSK show tubular function defects of acidification and concentration. These are considered to be secondary to morphological changes of collecting tubules. Primary distal renal tubular acidosis (dRTA) is a rare genetic disease caused by mutations in different genes involved in the secretion of H(+) ions in the intercalated cells of the collecting duct required for final excretion of fixed acids. Both autosomal dominant and autosomal recessive forms have been described, the latter is also associated with sensorineural hearing loss., Methods and Results: We report two patients presenting with dRTA, late sensorineural hearing loss and MSK, in whom molecular investigations demonstrated the presence of mutations of the H(+) proton pump ATP6V1B1 and ATP6V0A4 genes., Conclusions: These observations, including a previous description of a similar case in the literature, indicate that MSK could be a consequence of the proton pump defect, thus can potentially provide new insights into the pathogenesis of MSK.

Rabson-Mendenhall syndrome is a rare genetic disorder characterized by severe insulin resistance, extreme hyperinsulinemia, postprandial hyperglycemia, growth retardation, and dysmorphisms. Enlargement of the kidneys and nephrocalcinosis have been described previously. We report a 10-year-old boy who presented with gross hematuria, unilateral hydronephrosis, and the initial diagnosis of bilateral extensive medullary nephrocalcinosis. Medullary sponge kidney (MSK) was included in the differential diagnosis given the ultrasound findings. Further evaluation by intravenous pyelogram confirmed the suspected bilateral MSK. Given the patient's history of hydronephrosis due to an obstructing renal stone and MSK, urine calcium excretion was assessed and found to be markedly increased at 9.5 mg/kg per day. To our knowledge, this is the first report of Rabson-Mendenhall syndrome and an association with MSK. We recommend evaluation for nephrocalcinosis, MSK, and hypercalciuria in all children diagnosed with Rabson-Mendenhall syndrome.

Medullary cystic kidney disease type 1 (MCKD1) is an autosomal dominant, tubulo-interstitial nephropathy that causes renal salt wasting and end-stage renal failure in the fourth to seventh decade of life. MCKD1 was localized to chromosome 1q21. We demonstrated haplotype sharing and confirmed the telomeric border by a recombination of D1S2624 in a Belgian kindred. Since the causative gene has been elusive, high resolution haplotype analysis was performed in 16 kindreds. Clinical data and blood samples of 257 individuals (including 75 affected individuals) from 26 different kindreds were collected. Within the defined critical region mutational analysis of 37 genes (374 exons) in 23 MCKD1 patients was performed. In addition, for nine kindreds RT-PCR analysis for the sequenced genes was done to screen for mutations activating cryptic splice sites. We found consistency with the haplotype sharing hypothesis in an additional nine kindreds, detecting three different haplotype subsets shared within a region of 1.19 Mb. Mutational analysis of all 37 positional candidate genes revealed sequence variations in 3 different genes, AK000210, CCT3, and SCAMP3, that were segregating in each affected kindred and were not found in 96 healthy individuals, indicating, that a single responsible gene causing MCKD1 remains elusive. This may point to involvement of different genes within the MCKD1 critical region.

Of unknown pathogenesis, sponge kidney (SK) is variably associated with nephrocalcinosis, stones, nephronic tubule dysfunctions and precalyceal duct cysts. Amongst 72 unrelated renal SK patients with renal stone disease, we detected one with unilateral bifid renal pelvis and six with unilateral small kidneys (longitudinal diameter difference >15%). Secondary causes of small kidney were excluded. Of the seven cases, four had reduced renal function (67 vs 7% in the entire cohort), and three developed hyperparathyroidism during follow-up (43 vs 4%). The pathogenesis of SK ought to explain why anatomical structures of different embryological origin are involved (the precalyceal and collecting ducts and the nephron) and why there is frequent association with hyperparathyroidism. In embryogenesis, the metanephric blastema synthesizes the chemotactic glial-derived neurotrophic factor (GDNF) to prompt the ureteric bud to branch off from Wolff's mesonephric duct, and to approach and invade the blastema. The bud's tip expresses the GDNF receptor (RET). RET-GDNF binding is crucial not only for the correct formation of ureters and collecting ducts (both of Wolffian origin), but also for nephrogenesis. We advance the hypothesis that SK results from a disruption in the ureteric bud-metanephric blastema interface, possibly due to one or more mutations or polymorphisms of RET or GDNF genes. This would explain: the concurrent alterations in precalyceal ducts and the functional defects in the nephron, the occasional association with size and the functional asymmetry between the two kidneys, some degree of renal dysplasia causing the reduction in the glomerular filtration rate and (given the role of RET in parathyroid cell proliferation) the association with hyperparathyroidism.

The case histories of two Afro-Trinidadian brothers aged 8 and 11 years who developed end-stage renal disease (ESRD) are presented. Neither had had cause in the past to seek medical attention for any renal-related illness. At presentation both had anaemia, growth failure and other clinical and laboratory evidence of ESRD. Kidney histology in one child was consistent with familial juvenile nephronophthisis (NPH). This is a common cause of ESRD in children in other countries but it has not been recognized previously in Trinidadian and other West Indian children, and should be considered as a possible aetiology in West Indian children presenting with renal failure.

A case of simultaneous adult polycystic kidney disease and medullary sponge kidney is reported. Such an occurrence is rare but suggests that these two conditions share a common pathogenesis.

Two cases of simultaneous medullary sponge and adult polycystic kidney disease developed in siblings. The diagnoses of polycystic kidneys were made by renal ultrasonography and medullary sponge kidney was diagnosed roentgenographically. The family history was markedly positive for "cystic" disease. Medullary sponge kidney might be a precursor of polycystic kidney disease in some instances, or, more likely, this represents two separate afflictions occurring in the same individuals. When large medullary sponge kidneys are encountered, the possibility of concomitant polycystic kidney disease should be entertained and investigated with a sonogram. While the prognosis of isolated sponge kidney is excellent, polycystic kidney disease eventually leads to hypertension and renal failure.

The diagnosis of medullary sponge kidney ( MSK ) is usually made as an incidental finding on pyelogram. The essential abnormality of this condition is a " paintbrush " appearance of the calyces due to the presence of contrast within dilated collecting ducts. Since the radiologic features are similar to those of papillary necrosis, a history of analgesic abuse may make the differential diagnosis difficult. We describe a patient whose urogram strongly suggested MSK but who also had a history of analgesic abuse. Special studies demonstrating completely normal renal function and proven MSK in the patient's mother allowed the diagnosis of medullary sponge kidney. We reviewed the similarities and differences between MSK and papillary necrosis to identify features of diagnostic significance.

A family is presented in which four and possibly five members of a sibship of seven are affected with polycystic kidney with congenital hepatic fibrosis. The excretory urogram in this disease may be indistinguishable from that of medullary sponge kidneys. Therefore, it is suggested that family studies be undertaken when a diagnosis of medullary sponge kidney is made.

Many genetically determined cystic kidney disorders occur in children. Presenting manifestations related to the kidney include failure to thrive, abdominal enlargement or flank masses, progressive renal failure, or urinary tract infection. Radiological techniques often yield information helpful in establishing the type and extent of renal lesions. Cataloging the cystic renal disease in terms of genetic patterns, the involvement of liver or another organs, and the nature of the disorder of renal architecture is helpful in establishing the proper handling of affected children, and in genetic counseling.

It has become obvious that consideration of only pathological anatomy gives little insight into the pathogenesis of cystic kidney disease. Better markers are required before an adequate system of classification can be developed. Once nosologic separation has been effected, specific diseases can be studied in more detail and an attempt can be made to elucidate the fundamental molecular abnormality. Genetic factors may be extremely useful in defining discrete disease entities; unfortunately, they have been too frequently disregarded by workers in the field. If progress is to be made in the area of structural abnormalities of the kidney, the common efforts of nephrologists, pathologists, physiologists, and geneticists will be required.

Medullary sponge kidney was found in association with congenital absence of teeth (anodontia) in 3 siblings of a single family. Anodontia occurs in the rare familial syndrome of ectodermal dysplasia, but its association with a renal (mesodermal) anomaly is not known. The present report lends further support to a possible hereditary etiology for medullary sponge kidney.