Nephronophthisis

What is nephronophthisis?

Nephronophthisis is a progressive cystic kidney disease characterized by cysts (round sacs) developing in the kidneys.
Nephronophthisis is considered to be caused by structural and functional abnormalities of primary cilia in the kidney tubular cells, which result in structural and functional kidney disorders.
Nephronophthisis can be classified into three types: infantile nephronophthisis, which progresses to end-stage kidney disease (condition requiring dialysis or a kidney transplantation) at the age of around 3 to 5 years; juvenile nephronophthisis, which develops in infants or school-age children and progresses to end-stage renal disease at a median age of around 13 years; and adolescent nephronophthisis, which progresses to end-stage renal disease at a median age of around 19 years. Among these, juvenile nephronophthisis is said to be the most frequent form.

Symptoms of nephronophthisis

In nephronophthisis, the function of the kidney tubules to reabsorb water and nutrients is impaired, and as a result, the amount of urine increases, and a large amount of salt and water is lost. Consequently, the initial symptoms include polydipsia, polyuria, daytime urinary incontinence and bedwetting, and growth disorders (failure to thrive/short stature), and in juvenile nephronophthisis, these symptoms appear from the age of around 4 to 6 years. Nephronophthisis is rarely detected by urine test abnormalities, and a low specific gravity urine (low density urine) is observed. As renal dysfunction progresses, the amount of urine decreases, and hypertension and anemia occur. In addition, about 10% to 20% of patients with nephronophthisis present with extrarenal symptoms (e.g., eye manifestations,mental retardation, and skeletal and facial abnormalities), which lead to the detection of the disease in some patients. In particular, retinitis pigmentosa (the most common concurrent eye disease), eye movement disorders, liver fibrosis, abnormalities of the skeleton and facial expression, etc. may serve as clues for an early diagnosis.
A diagnosis is often difficult. Genetic testing can help making a diagnosis, but genetic abnormalities are found in only about 30% of patients. The diagnosis is made through a comprehensive evaluation of the symptoms listed above, as well as the results of echography,kidney biopsy (procedure to collect a piece of kidney tissue for examination), etc.

Treatment for nephronophthisis

To date, there is no current fundamental treatment for nephronophthisis. Drug therapy and diet therapy are currently provided, with priority put on delaying the time at which end-stage kidney disease begins. Drug therapy and diet therapy are also given to treat complications, including hypertension and anemia. Furthermore, treatment with growth hormone may be prescribed for a short stature due to kidney failure.

1) Drug therapy

  • Oral iron preparations or a hormone to produce red blood cells is periodically administered for anemia due to kidney failure.
  • Oral medications are taken to supplement the Vitamin D activity to regulate calcium and phosphorus that is lost due to kidney failure.
  • Medications are taken to prevent blood acidification due to kidney failure.
  • Medications to reduce blood pressure are taken for hypertension.
  • Growth hormone is injected for short stature lower than the reference height (i.e., ≤ -2.5 SD of the mean height).
  • Besides the above, medicines to lower uric acid and those to lower toxins triggering uremic symptoms (anorexia, itchiness, and nausea), which increase as the kidney function worsens, may be taken.

2) Nutrition

  • Necessary energy and protein based on one’s age should be taken.
  • Potassium and phosphorous intake may be restricted depending on the kidney function.
  • When the amount of urine is increased, a large amount of water and salt is lost, resulting in dehydration; therefore, sufficient amounts of water and salt should be taken. If the amount of urine decreases due to a reduced kidney function, salt intake will be restricted.

NephronophthisisQ&A

1) What is the approximate number of patients with this disease?

As of 2017, the number of patients is reported to be at least 130.

2) Is the cause of this disease known?

Abnormalities involving the NPHP gene are known to be the cause of this disease, but patients without any abnormalities in this gene have also been reported.

3) Is this disease hereditary?

It has mainly an autosomal recessive inheritance pattern, but sporadic cases (disease occurs sporadically and is not inherited by family members) have also been reported.

4) How much exercise is allowed?

The range of exercise allowed varies depending on the kidney function.
To maintain one’s kidney function, sufficient water and salt should be taken while doing exercise to prevent dehydration.

5) What is the clinical course of this disease?

All patients develop kidney failure by adulthood.
If the disease progresses to end-stage kidney disease, a renal replacement therapy will be provided to compensate for the renal dysfunction.
Renal replacement therapy includes dialysis (peritoneal dialysis/hemodialysis) and kidney transplantation (living/deceased donor kidney transplantation). Renal replacement therapy is selected according to the patient’s living environment and life plan based on a discussion between the treating doctor, patient, and family.

この病気に関する資料・関連リンク

  • 竹村司. 厚生労働科学研究費補助金(平成27年度厚生労働科学研究難治性疾患政策研究事業)分担報告書. 腎・泌尿器系希少・難治性疾患軍に関する診断基準・診療ガイドラインの確立. ネフロン癆
  • 杉本圭相. ネフロン癆-臨床像と診断に向けたアプローチ-. 日本小児腎臓学会雑誌. 30:2:112-118、 2017
  • 竹村司. 日本人ネフロン癆の臨床・遺伝的特徴. 日本小児腎臓学会雑誌. 28:2:107-113、 2015
  • 小児慢性特定疾病情報センター
    https://www.shouman.jp/disease/details/02_07_026/
  • 難病情報センター
    http://www.nanbyou.or.jp/entry/3279
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