About 10 months before we are born, we exist as a single cell, and subsequently a fertilized ovum. During human embryogenesis, all organs, including the kidneys, are created. Therefore, the kidney may theoretically be regenerated from induced pluripotent stem cells or embryonic stem cells that are biologically identical to the fertilized ovum, if they follow a developmental program. It has been thought that a program involved in organogenesis must be very complicated and that a huge number of molecules are involved; however, recent studies revealed that the process is less complicated than previously thought and only a few programs are required, because pluripotent stem cells are innately able to develop into complicated structures, through “self-organizing ability.” Kidney stem cells have this ability. Therefore, some researchers believe that it is possible to create kidneys from stem cells and have energetically pursued research in this field. In this article, I introduce these concepts and discuss what will be needed prior to clinical application.
Nephronophthisis (NPH) belongs to cystic renal diseases with the cystic formation in corticomedullary border of the kidney. NPH accounts for approximately 5% of end-stage renal disease occurring in childhood, is characterized by renal medullary cyst formation, tubulointerstitial nephritis accompanied by progressive glomerular sclerosis and hyalinization of glomeruli. NPH shows mainly autosomal recessive inheritance. Polyuria and polydipsia, and urinary concentration defect are demonstrated in early childhood (4–6 years of age). The urine often shows low specific gravity specific density and low-molecular-weight protein. Typical extrarenal manifestations are helpful for the diagnosis. NPHP1, the gene most often responsible for juvenile nephronophthisis, encodes the nephrocystin-1 molecule. However, NPHP gene mutation was found in about 30%. Recently, whole exome sequencing allows increased detection of mutation caused by NPH. Diagnostic criteria for NPH was provided in Japan, helping for the diagnosis for cases without definitive diagnosis in the future.
Drug-induced kidney injury is common in daily practice but it is difficult to diagnosis. Kidney is a major target organ for drugs because drugs are excreted through the kidney. Diagnosis of drug-induced kidney injury is made by clinical history and laboratory investigations including blood and urine tests, imaging studies and other specific examinations such as drug induced lymphocyte stimulation test and urine eosinophils, but a definite diagnosis is difficult. There is no specific therapy in most cases beyond hydration and/or dose adjustment patients with decreased kidney function.
It has been said that the guideline of American Academy of Pediatrics regarding voiding cystourethrography (VCUG) indication has possibility to overlook high grade Vesicoureteral reflux (VUR). In this article, we conducted a multi-center prospective observational study to identify risk factors during acute phase period for high grade VUR (Grade 3–5, VUR≥3) in infants with first urinary tract infection (UTI). The results of univariate analysis showed that abnormality of renal bladder ultrasound (RBUS), high serum CRP level and high serum procalcitonin (PCT) level at admission were the risk factors relating to VUR≥3 (p<0.01). Furthermore, the result of multivariate analysis showed that serum PCT≥0.37 ng/ml is the single factor relating to the VUR≥3 (odds ratio 29.3, 95%CI; 3.7–236.0, p<0.01). In conclusion, first UTI infants with PCT≥0.37 ng/ml should undergo VCUG because they are at high risk to complicate high grade VUR.
In pediatric patients with chronic renal failure, peritoneal dialysis (PD), which requires sanitary care by the family, is often selected. Therefore, it is necessary to ensure electricity, water, and a clean space. We investigated the effect of Kumamoto earthquake on seven patients treated with PD by pediatricians in Kumamoto prefecture in 2016. Power and water outages occurred in six patients’ houses; two were hospitalized; two performed continuous ambulatory peritoneal dialysis (CAPD) in a car or in an infirmary at evacuation shelters; one was evacuated outside the prefecture; and one was at home. Peritonitis or exit-site infection occurred in two patients in later days. Chiefly, regular prescribing dialysate fluids and fixtures for two weeks of stock caused no problems, and it was possible to get in touch with patients and provide a quick response. We propose three points as follows: 1) to prepare to carry out CAPD at home at any time, 2) to cooperate with local hospitals usually, and 3) to secure a dialysis environment and to recommend the hospital management as much as possible at the time of disaster.
We used the data from a school urine screening program conducted in Yonago, Tottori Prefecture, Japan, to investigate the prevalence of urinary abnormalities, final diagnoses, renal histologic diagnoses and prognoses of cases in which renal biopsy was performed. We also performed renal biopsies and assessed the renal histologic diagnoses and prognoses of cases identified by clinical symptoms. Between 1978 and 2016, 418,802 children were screened; of them, 2,567 underwent a tertiary examination. The number of children received a final diagnosis was decreased from a cumulative total of 84.2 per 10,000 persons to 4.50 before and after setting up of the judging committee of a school urine screening program, and the “normal” in a final diagnosis was reduced. Moreover, the “glomerulonephritis” in that fell from 3.1 to 0.76. We performed renal biopsy for 54 cases identified by a school urine screening program and 39 cases identified by clinical symptoms. The most common histological diagnoses were IgA nephropathy in cases found by the school urine screening program and purpura nephritis in cases identified by clinical symptoms. The judging committee of a school urine screening program in Yonago city contributed to an accuracy improvement of a school urine screening program.
A 15-year-old boy presented to our clinic with nycturia since a month. He had been diagnosed with steroid-dependent nephrotic syndrome at the age of 3 years and was since then being treated with oral prednisolone, cyclosporin (CsA), and azathioprine. A nocturnal urine concentration test was performed, which showed a urinary concentration disorder, with increased plasma arginine vasopressin. These findings indicated partial nephrogenic diabetes insipidus (NDI).
These were suspected to be the effects of CsA, the dose of which had been increased from the time the treatment began to his current age; hence, the CsA dose was reduced back to the initial dose. Following this, the symptoms disappeared immediately. CsA is used for immunosuppression in nephrotic syndrome. Its use has been associated with acute and chronic nephrotoxicity. CsA is also known to cause urinary concentration disorder and its mechanism has been recently reported to involve its relationship with aquaporin2. Pediatric nephrologists who frequently use CsA should understand that CsA is involved in water homeostasis. Drug-induced NDI is rare in children. NDI should be considered as a possibility in cases of nephrotic syndrome, especially in those who are on CsA therapy. Thus, we report a case of a 15-year-old boy with drug induced NDI during treatment of nephrotic syndrome.
Hypoalbuminemia is associated with the increased risk of thromboembolic complications in patients with the nephrotic syndrome. We report a case of a 13-year-old boy who was suggested proteinuria in a school urinary screening program, the serum albumin level was 2.7 g/dl and the urinary protein-to-creatinine ratio (UP/Cr) was 2.4 g/gCr at the admission. Five days later, he was diagnosed the nephrotic syndrome because the serum albumin level decreased to 2.5 g/dl. He received prednisolone (60 mg/day), and reached to remission on day 12 of hospitalization. There was hypercoagulable state such as FDP 9.0 μg/ml at the admission, and hypercoagulability was not improved after remission. There were no congenital thrombotic factor and antiphospholipid syndrome, but FDP increased to 13.2 μg/ml, and the platelet count also decreased to 13×104/μl on day 32 of hospitalization. A contrast-enhanced CT scan demonstrated bilateral pulmonary embolisms. Anticoagulant therapy with warfarin was stared, with dose adjustment according to PT values. Finally pulmonary embolisms were resolved without sequelae. In children with the nephrotic syndrome, we should carefully consider thrombosis and check the imaging test when hypercoagulability is not improved, even if low serum albumin levels are not severe.
Many cases of prostatic cystic disease are asymptomatic and are found incidentally by imaging examination. We encountered a case of utricular cyst with urinary tract infection. A one-year-old boy presented at our hospital with fever, crying on urination and abnormal urine odor. Laboratory findings revealed pyuria, and elevated white blood cell count and creactive protein level. Ultrasonography, computed tomography and magnetic resonance imaging showed a cystic lesion of approximately 40 mm diameter in his pelvis. The urinary tract infection improved after treatment with antibiotics and the cyst was anatomically diagnosed as a utricular cyst on the basis of cystourethroscopic findings. The cyst could not be confirmed 4 months after continuous prophylactic administration of antibiotics so surgical resection was not required. Although antibiotic prophylaxis has been discontinued for more than 1 year, there is no sign of recurrence to date. Urinary tract infections in childhood are sometimes complicated by congenital urological abnormalities. Therefore, the kidney and urinary tract system of children with upper-urinary tract infections may need to be examined. Utricular cysts are not often detected in childhood, but it is important for us to consider utricular cysts as a possible complication of urinary tract infection.
BK virus is associated with hemorrhagic cystitis, ureteritis, ureteral stenosis and renal dysfunction with interstitial nephritis in immunocompromised patients. Hemorrhagic cystitis is a characteristic symptom in patients with BKV infection receiving bone marrow transplant. Here, we report the patient of BKV nephropathy after cord blood stem cell transplantation whose initial manifestation was renal dysfunction with interstitial nephritis without hemorrhagic cystitis. A 12-year-old girl with acute lymphoblastic leukemia was treated with cord blood stem cell transplantation because of treatment failure of chemotherapy. On the 13th day after transplantation, decoy cells were detected in urine sediment and increase of urine and blood BKV copy numbers was observed. The diagnosis of BKV nephropathy was made and confirmed by renal biopsy. Tacrolimus was withdrawn and stopped but renal dysfunction was not improved. High dose intravenous immunoglobulin was administered and her renal dysfunction was improved. The patient of BKV nephropathy without hemorrhagic cystitis is rare, but physicians should differentiate BKV nephropathy from other causes of renal dysfunction after stem cell transplantation such as transplantation related treatment including chemotherapy, antibiotics and immunosuppressive drugs.
Acute tubular necrosis is well known to develop as an ischemic renal injury in neonates. We experienced a rare case of renal papillary necrosis (RPN). A boy was born with severe asphyxia due to rupture of vasa previa. He had severe anemia, acidemia, and unmeasurable blood pressure, indicating hypovolemic shock. After 2 days of anuria associated with acute kidney injury (AKI), hematuria was observed. Intraurethral catheter was repetitively obstructed by necrotic debris or blood clot, resulting in hydronephrosis. On 14 days after birth, abdominal echo and MRI revealed multiple hemorrhagic cystic lesions in both kidney. The cystic lesions gradually diminished and disappeared. The characteristic images support a diagnosis of renal papillary necrosis. This case is informative to consider the pathogenesis of RPN as ischemic AKI.