| name | description | evidence |
|---|---|---|
| Infantile Nephronophthisis | Early onset in infancy characterized by rapid progression to end-stage renal disease. | TRUNCATED |
| Juvenile Nephronophthisis | Most common form with onset in childhood and progressive renal failure by adolescence. | TRUNCATED |
| Adolescent Nephronophthisis | Later onset in teenage years with slower progression to renal failure. | TRUNCATED |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:29717526 | NO_EVIDENCE | Nephronophthisis is an autosomal recessive cystic kidney disease and one of the most common genetic disorders causing end-stage renal disease in children. Nephronophthisis is a genetically heterogenous disorder with more than 25 identified genes. In 10%-20% of cases, there are additional features of a ciliopathy syndrome, such as retinal defects, liver fibrosis, skeletal abnormalities, and brain developmental disorders. | The provided literature discusses the genetic heterogeneity and associated features of nephronophthisis but does not provide information about its global prevalence. |
| PMID:25514144 | NO_EVIDENCE | According to the official health statistics, Taiwan has the highest prevalence of end stage renal disease (ESRD) in the world. Each year, around 60,000 ESRD patients in Taiwan consume 6% of the national insurance budget for dialysis treatment. The prevalence of chronic kidney disease (CKD) has been climbing during 2008-2012. | The article discusses the prevalence of end-stage renal disease in Taiwan but does not provide specific prevalence rates for nephronophthisis. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:19118152 | SUPPORT | Nephronophthisis (NPHP), a recessive cystic kidney disease... Mutations in NPHP genes cause defects in signaling mechanisms that involve the noncanonical Wnt signaling pathway and the sonic hedgehog signaling pathway, resulting in defects of planar cell polarity and tissue maintenance. | The provided snippet indicates that mutations in NPHP genes affect mechanisms that disrupt cellular functions related to cilia, supporting the statement that these mutations lead to impaired cilia. |
| PMID:34183231 | SUPPORT | Mutations in genes encoding centriolar or ciliary proteins cause diseases collectively known as 'ciliopathies'. | This statement refers to how ciliary protein gene mutations cause related ciliopathies, aligning with impaired cilia as seen in Nephronophthisis. |
| PMID:21113628 | SUPPORT | Ciliary dysfunction has emerged as a common factor underlying the pathogenesis of both syndromic and isolated kidney cystic disease, an observation that has contributed to the unification of human genetic disorders of the cilium, the ciliopathies. | The excerpt affirms that ciliary dysfunction is fundamental to the development of various cystic kidney diseases, including Nephronophthisis, caused by mutations affecting cilia. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:19186246 | PARTIAL | Their importance for key developmental pathways such as Sonic Hedgehog (Shh) and Wnt is beginning to emerge. The function of nodal cilia, for example, is vital for breaking early embryonic symmetry, Shh signaling is important for tissue morphogenesis and successful Wnt signaling for organ growth and differentiation. When ciliary function is perturbed...brains form improperly. | This reference supports the idea that disrupted cilia function affects the Wnt and Hedgehog pathways, but it does not specify nephronophthisis directly. |
| PMID:22206729 | SUPPORT | Mutations of the ankyrin-repeat protein Inversin, a member of a diverse family of more than 12 proteins, cause nephronophthisis (NPH)...Most NPH gene products (NPHPs) localize to the cilium, and appear to control the transport of cargo protein to the cilium by forming functional networks. | This reference directly links nephronophthisis to defective cilia and mentions involvement in pathways like Wnt signaling. |
| PMID:24162855 | PARTIAL | The primary cilium, a microtubule-based organelle that can serve as a signaling antenna, has been demonstrated to have a significant role in ensuring correct kidney development and function...one of the signaling pathways that requires the cilium for normal development is Wnt signaling. | This reference supports the involvement of the primary cilium in Wnt signaling but does not explicitly connect it to nephronophthisis. |
| PMID:20544799 | PARTIAL | Absence of the sonic hedgehog (shh) ligand is associated with the midline defect holoprosencephaly...mutation of proteins required for function of cilia often leads to impaired Shh signaling and disruption of neural tube closure. | This reference supports the idea that ciliary dysfunction affects Hedgehog signaling but focuses on neural tube defects rather than nephronophthisis. |
| PMID:35655331 | SUPPORT | Ciliary dysfunction causes many human conditions termed ciliopathies...ciliopathy spectrum could be the poster child for advances and challenges in Mendelian human genetics over the past half century...illustrates many core concepts of human genetics. | This reference supports the concept that defects in the primary cilia affect key signaling pathways, including the ones mentioned, in the context of nephronophthisis. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:21071979 | PARTIAL | Nephronophthisis is a recessive disorder of the kidney that is the leading cause of end-stage renal failure in children. Through positional cloning, many of the causative mutations have been mapped to genes involved in centrosome and cilia function. | The literature supports that nephronophthisis is related to ciliary dysfunction, but it does not explicitly mention polyuria and polydipsia as part of its pathophysiology. |
| PMID:16186680 | PARTIAL | Renal tubular disorders may affect multiple (e.g., Fanconi syndrome) or specific (e.g., nephrogenic diabetes insipidus, renal glucosuria) tubular functions. Most conditions are primary and monogenic but occasionally are secondary to other disorders. | The reference discusses renal tubular disorders, which can result in polyuria and electrolyte imbalance, but it does not explicitly link these to ciliary dysfunction in nephronophthisis. |
| PMID:9790573 | PARTIAL | Cysts originate within the glomeruli and all tubular structures, and their growth is the result of proliferation of incompletely differentiated epithelial cells and the accumulation of fluid within the cysts. | While the reference discusses fluid accumulation and cyst formation in polycystic kidney disease, it does not directly link these to nephronophthisis or explicitly mention polyuria. |
| PMID:18312782 | PARTIAL | Overlapping clinical entities including situs inversus, certain infertility disorders, as well as chronic respiratory infections have their roots in abnormal ciliary function. | This reference supports the involvement of ciliary dysfunction in various disorders but does not provide specific details on nephronophthisis and its pathophysiology related to polyuria and polydipsia. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:35533128 | SUPPORT | Diagnosis is made by a positive genetic test, or a kidney biopsy demonstrating chronic tubulointerstitial changes with thickening of the tubular basement membranes. | The diagnosis of nephronophthisis includes tubulointerstitial changes, which aligns with chronic tubular dysfunction and inflammation leading to interstitial fibrosis. |
| PMID:31399984 | PARTIAL | Renal interstitial lymphangiogenesis is found in patients with chronic kidney disease (CKD) and a series of animal models of renal fibrosis. | While the study focuses on lymphangiogenesis, it mentions renal interstitial fibrosis related to chronic kidney disease, of which nephronophthisis is a type. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:16966065 | WRONG_STATEMENT | Nephronophthisis is a chronic tubulo-interstitial nephritis which progress to terminal renal failure. | The statement claims that abnormal cell proliferation and differentiation result in cyst formation in nephronophthisis, but the literature describes nephronophthisis as a chronic tubulo-interstitial nephritis without indicating cyst formation due to abnormal cell proliferation and differentiation as a characteristic pathophysiological mechanism. Instead, it mentions cortical microcysts in infantile forms but emphasizes interstitial fibrosis and tubular basement membrane changes. |
| PMID:25575298 | NO_EVIDENCE | Almost all proteins associated with a broad spectrum of human cystic kidney diseases have been localized to the region in or around the cilia. | While this reference discusses abnormal cilia structure and function in cystic kidney diseases, it does not specifically address nephronophthisis or the mechanism of abnormal cell proliferation and differentiation leading to renal cyst formation in nephronophthisis. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:16966065 | SUPPORT | Nephronophthisis is a chronic tubulo-interstitial nephritis which progress to terminal renal failure... Histologic lesions concern tubular basement membranes which are thickened and multilayered or thinned. There is an associated interstitial fibrosis. | The provided excerpt mentions chronic tubulo-interstitial nephritis (tubular dysfunction and interstitial fibrosis) and progression to terminal renal failure, supporting the statement that these factors contribute to ESRD. |
| PMID:10352410 | PARTIAL | Progressive renal disease poses an increasing problem for the medical community. Though the causes of end-stage renal failure are multiple, the histologic pictures of chronic renal disease are remarkably similar being characterized by interstitial infiltration, fibrosis, tubular atrophy and dilatation. | This literature indicates the role of interstitial infiltration, fibrosis, and tubular atrophy leading to ESRD, which partially overlaps with the factors mentioned in the statement. However, cyst formation specific to nephronophthisis was not explicitly mentioned. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:35533128 | PARTIAL | Nephronophthisis is an autosomal recessive cystic kidney disease caused by mutations in genes that encode proteins involved in the primary cilia function, resulting in kidney disease and extrarenal manifestations such as retinal degeneration and liver fibrosis. | The literature supports the involvement of the liver and retina in nephronophthisis but does not mention the brain specifically in this context. |
| PMID:32432520 | PARTIAL | Senior-Loken syndrome (SLS) is a rare autosomal recessive disease characterised by nephronophthisis and retinal degeneration, and belongs to a group of genetically heterogeneous disorders known as the ciliopathies. | The literature supports the involvement of the retina in Senior-Loken syndrome but does not mention the liver or brain specifically in this context. |
| PMID:33306870 | SUPPORT | Senior-Loken syndrome is a rare genetic disorder that presents with nephronophthisis and retinal degeneration, leading to end-stage renal disease and progressive blindness. | The literature supports the involvement of the retina in Senior-Loken syndrome, which is a form of nephronophthisis. |
| PMID:35655331 | NO_EVIDENCE | The JS phenotype alone is caused by pathogenic variants in more than 40 genes; remarkably, all of the associated proteins function in and around the primary cilium. | This reference discusses the involvement of primary cilia in a broader sense but does not specify the extrarenal manifestations like those in Senior-Loken syndrome. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:34828368 | SUPPORT | NPHP gene types present with some common pathophysiological features alongside a diverse range of extra-renal phenotypes associated with specific syndromic presentations. | The reference states that there is diversity in pathophysiological features and extra-renal phenotypes among different NPHP gene types, which supports the statement that the age of onset and rate of progression vary. |
| PMID:35570616 | SUPPORT | Nephronophthisis is the most common genetic cause of kidney failure in childhood....Treatment for nephronophthisis is symptomatic, and kidney transplant is a good treatment option when kidney failure has developed. | While this reference highlights the general management of nephronophthisis, it implies variability in progression and severity since not all individuals progress to kidney failure at the same rate. |
| PMID:35922195 | SUPPORT | All 6 children progressed to end-stage renal disease (ESRD) within 10 (4, 65) months of onset. | The reference indicates variability in the progression to end-stage renal disease, supporting the statement regarding variable progression rates depending on the specific NPHP gene mutations. |
| PMID:16966065 | SUPPORT | There are three main clinical forms of nephronophtisis which have been associated with five gene defects. Juvenile nephronophtisis, the most frequent, progress to end stage renal failure before age 15. | This reference identifies different clinical forms of nephronophthisis, which progress at different rates, thus supporting the statement on variability in age of onset and progression. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:16966065 | SUPPORT | Nephronophthisis is a chronic tubulo-interstitial nephritis which progresses to terminal renal failure. | This abstract describes nephronophthisis as a progressive renal disease leading to end-stage renal failure, supporting the idea that progressive renal failure is a frequent and diagnostic feature. |
| PMID:33323469 | SUPPORT | Nephronophthisis-related ciliopathies (NPHP-RC) account for the majority of cases of monogenetically caused end-stage renal disease (ESRD) in children. | This reference states that nephronophthisis-related ciliopathies are a common cause of end-stage renal disease in children, confirming that progressive renal failure and progression to ESRD is common. |
| PMID:20969579 | SUPPORT | A Mendelian inheritance underlies a nonnegligible proportion of hereditary kidney diseases, suggesting that the encoded proteins are essential for maintenance of the renal function. | While the abstract primarily discusses hereditary kidney diseases in general, it emphasizes the importance of kidney function maintenance in genetic diseases, indirectly supporting the frequency and importance of progressive renal failure in conditions like nephronophthisis. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:17647025 | NO_EVIDENCE | Among the causes of secondary hypertension are a group of disorders with a Mendelian inheritance pattern. Recent advances in molecular biology have unveiled the pathogenesis of hypertension in many of these conditions. | While this reference mentions Mendelian forms of hypertension, there is no specific mention of Nephronophthisis resulting in hypertension or cardiovascular phenotypes generally. |
| PMID:20969579 | NO_EVIDENCE | A Mendelian inheritance underlies a nonnegligible proportion of hereditary kidney diseases, suggesting that the encoded proteins are essential for maintenance of the renal function. | This reference discusses hereditary kidney diseases and the genetic mutations involved but does not mention Nephronophthisis or its cardiovascular phenotypes including hypertension. |
| PMID:12589180 | NO_EVIDENCE | Defective transduction of the dopamine receptor signal in the kidney... | The article discusses the role of dopamine in the kidney and its involvement in hypertension, but it does not address Nephronophthisis or whether hypertension is a common cardiovascular phenotype in this condition. |
| PMID:23402468 | NO_EVIDENCE | Hypertension is the most common modifiable risk factor for cardiovascular disease. Antihypertensive treatment substantially reduces the risk of heart failure, stroke, and myocardial infarction. | This article offers a general overview of hypertension and its management but does not specifically mention Nephronophthisis or any associated cardiovascular phenotypes. |
| PMID:16336577 | NO_EVIDENCE | Nephrosclerosis, benign nephrosclerosis, and hypertensive kidney disease are terms that clinicians use when renal damage is thought to be secondary to essential hypertension. | While the article discusses hypertension in the context of renal diseases, it does not specify an association between Nephronophthisis and hypertension as a cardiovascular phenotype. |
| PMID:37910243 | NO_EVIDENCE | Hypertension is common in children with CAKUT and increases the risk of CKD. | This study focuses on congenital anomalies of the kidney and urinary tract (CAKUT) and their association with hypertension, but it does not discuss Nephronophthisis. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:35533128 | SUPPORT | Nephronophthisis is an autosomal recessive cystic kidney disease caused by mutations in genes that encode proteins involved in the primary cilia function, resulting in kidney disease and extrarenal manifestations such as retinal degeneration and liver fibrosis. | The literature mentions liver fibrosis as an extrarenal manifestation of nephronophthisis, supporting the statement that hepatic fibrosis is an occasional phenotype category of nephronophthisis. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:16966065 | SUPPORT | Some children present with extrarenal symptoms: tapetoretinal degeneration (Senior-Loken syndrome)... | This reference indicates that tapetoretinal degeneration, synonymous with retinitis pigmentosa in the context of this disease, is an occasional extrarenal symptom of nephronophthisis. |
| PMID:25161209 | SUPPORT | The renal lesions were characterized by diffuse renal cyst development with tubulointerstitial nephropathy...These renal and retinal lesions are most similar to those associated with nephronophthisis (NPHP) and retinitis pigmentosa in humans. | This reference directly confirms the association between nephronophthisis and retinitis pigmentosa as occasional ophthalmologic phenotypes. |
| PMID:37644229 | SUPPORT | At least 10% of NPHP cases present with extrarenal conditions, which most often include retinal degeneration. | This indicates that ophthalmologic phenotypes, including retinitis pigmentosa, occur occasionally in cases of nephronophthisis. |
| name | presence | evidence |
|---|---|---|
| Serum Creatinine | Elevated | TRUNCATED |
| Elevated Blood Urea Nitrogen (BUN) | Elevated | TRUNCATED |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:15138899 | SUPPORT | Two siblings affected with a mild form of JS were found to have a homozygous deletion of the NPHP1 gene identical, by mapping, to that in subjects with NPHP alone. | The NPHP1 gene deletion is associated with juvenile nephronophthisis, confirming the genetic link between NPHP1 and nephronophthisis. |
| PMID:36990420 | SUPPORT | Patients with pathogenic variants in CEP290 or IQCB1 presented early with retinopathy, whereas other patients with INVS, NPHP3, or NPHP4 variants first developed nephropathy. | This reference supports the genetic association of nephronophthisis with variants in several genes, highlighting NPHP1 among the genes associated with nephropathy. |
| reference | supports | snippet |
|---|---|---|
| PMID:34212438 | SUPPORT | we detected a homozygous predicted synonymous allele in NPHP3 in two children with hepatorenal fibrocystic disease from a consanguineous family. |
| PMID:26184788 | SUPPORT | Eight of 17 (47.1%) patients detected were identified to have mutations in NPHP3. |
| PMID:36990420 | SUPPORT | Patients with pathogenic variants in CEP290 or IQCB1 presented early with retinopathy, whereas other patients with INVS, NPHP3, or NPHP4 variants first developed nephropathy. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:14750102 | SUPPORT | Nephronophthisis (NPH) is an autosomal recessive kidney disease... Four genes responsible for different types of NPH have been identified: NPHP1, NPHP2, NPHP3, and NPHP4. | The literature identifies NPHP4 as one of the genes responsible for different types of Nephronophthisis. |
| PMID:34591160 | SUPPORT | Nephronophthisis (NPHP) 4 gene encoding nephrocystin-4... contributes to end-stage renal disease in children and young adults. | The literature indicates that NPHP4 is associated with end-stage renal disease in Nephronophthisis, highlighting its pathogenic role. |
| PMID:36990420 | SUPPORT | Senior-Loken syndrome (SLSN) is an autosomal recessive disorder characterized by retinopathy and nephronophthisis... Patients with pathogenic variants in CEP290 or IQCB1 presented early with retinopathy, whereas other patients with INVS, NPHP3, or NPHP4 variants first developed nephropathy. | The literature mentions that patients with NPHP4 variants develop nephropathy in the context of Nephronophthisis. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:15917209 | REFUTE | There has been tremendous progress in the past few years in understanding the molecular basis of nephronophthisis, and it is now evident that the disease is characterized by both clinical and genetic heterogeneity. | This indicates that Nephronophthisis is primarily driven by genetic mutations, not environmental factors. |
| PMID:20844548 | REFUTE | Nephronophthisis (NPHP) 4 gene coding nephrocystin-4 is involved in the development of renal tubules and its congenital mutations cause juvenile end-stage renal disease, NPHP. | This further supports that Nephronophthisis is caused by genetic mutations and not by environmental factors. |
| PMID:29869359 | REFUTE | The patient had elevated liver enzymes and biopsy-proven liver fibrosis. As liver synthesis was acceptable, only KT was performed. However, liver fibrosis progressed at 1.5 years after transplantation, manifested with portal hypertension and hypersplenism. | This case study describes genetic mutations as the cause of disease progression, reinforcing that Nephronophthisis is genetically driven. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:32906116 | SUPPORT | Nephronophthisis (NPHP) is an autosomal recessive disease manifesting as tubulointerstitial nephritis uniformly progressing to ESRD in approximately 5-10% patients in childhood. Living donor transplantation is the most beneficial mean of renal replacement therapy compared to other methods. | The abstract discusses that Nephronophthisis often leads to end-stage renal disease (ESRD) and mentions living donor transplantation as a beneficial renal replacement therapy option. |
| PMID:15715116 | SUPPORT | Diabetes and ESRD receiving Renal Replacement Therapy (RRT)... The main choices of modalities are: 1) haemodialysis (HD), 2) Peritoneal dialysis (PD), 3) Kidney transplantation alone (KTA) or 4) simultaneous kidney and pancreas transplantation (SPKT). | Although this reference focuses on diabetic nephropathy, it supports the statement that renal replacement therapies for ESRD include dialysis and kidney transplantation. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:36224286 | PARTIAL | Chronic kidney disease (CKD) is one of the strongest risk factors for hypertension, and hypertension can exacerbate the progression of CKD... therefore, one of the best strategies to slow the progression of CKD is to maintain the 'numbers' of these essential components necessary to preserve renal function. To this end, both the achievement of an optimal blood pressure and a maximum reduction in urinary protein excretion are essential. | This source suggests that managing blood pressure is essential in the context of CKD, which is related to nephron function. However, it does not explicitly mention Nephronophthisis, a specific type of nephropathy. |
| PMID:30354828 | NO_EVIDENCE | Resistant hypertension (RH) is defined as above-goal elevated blood pressure (BP) in a patient despite the concurrent use of 3 antihypertensive drug classes...evaluation includes identification of contributing lifestyle issues, detection of drugs interfering with antihypertensive medication effectiveness, screening for secondary hypertension, and assessment of target organ damage. Management of RH includes maximization of lifestyle interventions, use of long-acting thiazide-like diuretics (chlorthalidone or indapamide), addition of a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and, if BP remains elevated, stepwise addition of antihypertensive drugs with complementary mechanisms of action to lower BP. | This source provides comprehensive information on the evaluation and management of resistant hypertension but does not discuss Nephronophthisis specifically. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:35533128 | SUPPORT | At the moment there is no healing therapy, so early kidney transplant is a fundamental tool to improve prognosis. | There is no curative treatment for nephronophthisis, indicating that supportive care, including symptomatic treatment and monitoring, is currently applied to manage associated complications. |
| name | evidence | description |
|---|---|---|
| Autosomal Recessive | TRUNCATED | None |
| Tubulointerstitial Fibrosis | TRUNCATED | Progressive fibrosis of the kidney's tubulointerstitial region. |