Safety in glomerular numbers

Schreuder, Michiel F.

doi:10.1007/s00467-012-2169-x

Cited by 73 publications

(63 citation statements)

References 52 publications

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“…An impaired GFR is a relatively late phenomenon in children with a solitary functioning kidney, because the first signs of renal injury generally include hypertension and (micro)albuminuria (5). Monitoring for renal injury in children with a solitary functioning kidney and a normal initial estimated GFR, therefore, should focus on BP and determination of (micro)albuminuria, which can both be done noninvasively.…”

Section: Discussionmentioning

confidence: 99%

“…As a result, nephrons are formed until the 34th to 36th gestational week, without the possibility of additional nephron formation later in life (5). This finding implies that the total of number of nephrons at birth, approximately 900,000 nephrons per kidney with a high interindividual variability (6), should last the entire lifespan of an individual.…”

Section: Causes Renal Developmentmentioning

confidence: 99%

“…Moreover, drug administration in the prematurely born neonate with a solitary functioning kidney can have detrimental effects on nephrogenesis and GFR, especially when administered before the 28th gestational week (5). The most commonly used drugs that disturb nephrogenesis are aminoglycosides and nonsteroidal anti-inflammatory drugs (22).…”

Section: Environmental Factorsmentioning

confidence: 99%

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Clinical Implications of the Solitary Functioning Kidney

Westland

Schreuder

Goudoever

et al. 2014

Clinical Journal of the American Society of Nephrology

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Congenital anomalies of the kidney and urinary tract are the major cause of ESRD in childhood. Children with a solitary functioning kidney form an important subgroup of congenital anomalies of the kidney and urinary tract patients, and a significant fraction of these children is at risk for progression to CKD. However, challenges remain in distinguishing patients with a high risk for disease progression from those patients without a high risk of disease progression. Although it is hypothesized that glomerular hyperfiltration in the lowered number of nephrons underlies the impaired renal prognosis in the solitary functioning kidney, the high proportion of ipsilateral congenital anomalies of the kidney and urinary tract in these patients may further influence clinical outcome. Pathogenic genetic and environmental factors in renal development have increasingly been identified and may play a crucial role in establishing a correct diagnosis and prognosis for these patients. With fetal ultrasound now enabling prenatal identification of individuals with a solitary functioning kidney, an early evaluation of risk factors for renal injury would allow for differentiation between patients with and without an increased risk for CKD. This review describes the underlying causes and consequences of the solitary functioning kidney from childhood together with its clinical implications. Finally, guidelines for follow-up of solitary functioning kidney patients are recommended.

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Section: Discussionmentioning

confidence: 99%

Section: Causes Renal Developmentmentioning

confidence: 99%

Section: Environmental Factorsmentioning

confidence: 99%

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Clinical Implications of the Solitary Functioning Kidney

Westland

Schreuder

Goudoever

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…This is a plausible explanation as reduced nephron endowment has long been postulated to correlate with risk for hypertension as well as renal disease. 33 In contrast to the HSRA model, many studies using other models of congenital solitary kidney (rat 34 or pig 35 ) have observed compensatory nephrogenesis (i.e., increased nephron number). Similarly, studies in a novel sheep fetal nephrectomy model also demonstrated compensatory nephrogenesis.…”

Section: Discussionmentioning

confidence: 99%

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

Wang¹,

Johnson²,

White³

et al. 2015

Journal of the American Society of Nephrology

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Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney.

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“…It has been hypothesized that low birth weight or early life damage may have an impact on the kidney and its functions in later life [2,3]. It has already been shown that environmental influences during nephrogenesis, including growth restriction and medications, have a significant impact on final nephron numbers [4]. Nephrons are formed from the 5th gestational week onwards and formation ends around the 34th-36th week of gestation in humans [5].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats

Bueters

Jeronimus-Klaasen²,

Maicas³

et al. 2016

Nephron

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Background: Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Methods: Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. Results: Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 ± 0.32 vs. 5.0 ± 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 ± 3,468 vs. 30,527 ± 4,096; p = 0.026), higher creatinine clearance (0.84 ± 0.1 vs. 0.77 ± 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 µmol/l; p = 0.043) at 9 months. Conclusion: Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings.

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Safety in glomerular numbers

Cited by 73 publications

References 52 publications

Clinical Implications of the Solitary Functioning Kidney

Clinical Implications of the Solitary Functioning Kidney

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats

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