Part Ⅰ：Current Management Of Patients With Acquired Solitary Kidney

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Ekamol Tantisattamo1,2,3, Donald C. Dafoe4, Uttam G. Reddy1,2, Hirohito Ichii4, Connie M. Rhee1,2, Elani Streja1,2, Jaime Landman5, and Kamyar Kalantar-Zadeh1,2,6

Persons with an acquired solitary kidney, including those who have had a unilateral nephrectomy for living kidney donation, renal malignancies, or trauma, have decreased renal mass that leads to increased intraglomerular pressure and glomerular hyperfiltration. These physiologic adaptations of the solitary kidneys may exacerbate other preexisting and genetic conditions that could create a predisposition to or worsen glomerular pathologies, leading to unfavorable renal outcomes. Hence, these persons may benefit from special care and lifestyle modifications, including nutritional interventions. There is a lack of consensus and evidence for proper surveillance and management after nephrectomy, and misconceptions in both directions of having a “ normal ” versus “abnormal ” kidney status may cause confusion among patients and healthcare providers pertaining to long-term kidney health monitoring and management. We have reviewed available data on the impact of lifestyle modifications, particularly nutritional measures, and pharmacologic interventions, on short and long-term outcomes after nephrectomy. We recommend avoidance of excessively high dietary protein intake (>1 g/kg per day) and high dietary sodium intake (>4 grams/d), adequate dietary fi ber intake from plant-based foods, a target body mass index of <30 kg/m2 (in non-athletes and non-bodybuilders), and judicious management of risk factors of progressive chronic kidney disease (CKD), and future studies should help to better determine optimal care practices for these persons.

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Chronic kidney disease, which exists in over 10% of adults with 2 kidneys, can develop in persons with a solitary kidney and may progress to end-stage renal disease (ESRD) resulting in high physical and psychological burdens in addition to extraordinary healthcare costs. Whereas in the past, nephrectomy for living kidney donation was considered to be safe without a higher likelihood of CKD,1 more recent data suggest that there is a 3–5 times higher relative risk of ESRD after unilateral nephrectomy, while the absolute risk remains small.2–4 The pathogenesis of CKD and ESRD in kidney donors with a solitary kidney may be different from that in those chronic kidney disease patients without nephrectomy. Glomerulonephritis appears to be the most common renal disease, leading to early ESRD in living kidney donors, and underlying genetic predispositions may contribute to the faster progression of CKD to ESRD in some groups of living kidney donors.5 Misconceptions in both directions of having a “normal” versus “abnormal” kidney status cause confusion among patients and healthcare providers about long-term management.

According to the conventional definition and staging of chronic kidney disease, persons with only one kidney from congenital or acquired causes, such as donor nephrectomy, are classified as CKD patients. Physiological adaptation in the solitary kidney leads to higher glomerular filtration rates (GFRs) relative to units of the nephron, which can initially increase GFR, known as glomerular hyper- filtration, but in the long-term, it may lead to a gradual decline in kidney function, and this trend can happen even in living kidney donors. The progression to ESRDmay be related to unrevealed intrinsic risks of kidney diseases such as genetic aberrations.6 The resultant burden on kidney health, particularly if aggravated by other causes of glomerular hyperfiltration, such as high dietary protein intake, may lead to de novo glomerular diseases such as secondary focal segmental glomerulosclerosis (FSGS) and may accelerate other preexisting glomerular pathologies. Similar to most other causes of chronic kidney disease, the clinical manifestation of the solitary kidney is silent. Therefore, initial screening for signs of worsening renal function and accurately determining renal function is warranted. In addition to usual approaches for chronic kidney disease management, lifestyle modification including nutritional and dietary interventions can be considered for persons with a solitary kidney and may be complemented by certain pharmacologic interventions, as reviewed in this article.

Epidemiology of Solitary Kidney

Congenital solitary kidney, also known as unilateral renal agenesis, occurs in a ratio of about 1:1000, often on the left, with a male-to-female ratio of 1.8:1.7 Acquired solitary kidney after unilateral radical nephrectomy in adults is mainly due to living kidney donation, renal tumor, and trauma. Over the last 30 years, the rate of living kidney donation had gradually increased from 1800 donations in 1998 to 6600 donations in 2004. However, it has decreased since 2011 and has been stable at around 5650 kidney donations per year.8 The most common age range of living kidney donors is 35 to 49 years.9 The incidence of renal cell carcinoma is 63,990 cases each year. The risk for developing renal cancer significantly increases in individuals aged >60 years, and males are at an almost 2 times greater risk than females.10 There were 10,123 and 4299 radical nephrectomies performed during 1991–2002 and 1992–2007, respectively, due to renal cell carcinoma.11 The incidence of renal trauma is varied. One study reported 757 radical nephrectomies among 9002 renal trauma patients from 2002–to 2007.12 Young adult males are the most commonly affected population.

Pathophysiological Changes in Patients With a Solitary Kidney

GFR is correlated with the number of nephrons, and it may vary by age, gender, and body habitus. Loss of nephrons is usually not a cause of decreased GFR, owing to compensatory mechanisms, although these do not provide full compensation, and GFR increases to 65%– 70% of pre-donation GFR in healthy donors aged <60years.13 Since the excretory function of the kidney is needed to maintain fluid, electrolyte, and mineral balances, physiological adaptation occurs immediately after nephrectomy, with increases in effective renal plasma flow, glomerular ultrafiltration coefficient (Kf), and transcapillary hydraulic pressure gradient (DP), leading to increased single-nephron GFR, glomerular hyper- filtration, and overall increased GFR.14,15

In addition to renal hemodynamic change after nephrectomy, structural nephron alteration in the form of both hypertrophy and hyperplasia may occur.16 This compensatory glomerular hypertrophy is involved in several pathways including activation in mammalian target of rapamycin complex (mTOR), interleukin 10, and transforming growth factor-b.17 However, this compensatory mechanism post nephrectomy in living kidney donors differs from patients after nephrectomy for other reasons.18. The compensatory glomerular hyperfiltration can cause damage to the solitary kidney in the long term, especially if other factors would aggravate glomerular hyperfiltration, such as high dietary protein intake resulting in afferent arteriole dilation and leading to intraglomerular hypertension, or high dietary sodium intake resulting in increases in systemic hypertension and volume retention.19,20 Intraglomerular hypertension causes podocyte injury and loss of perm-selectivity of the filtrating function of the slit diaphragm between foot processes, causing proteinuria. In addition, endothelial- mesangial hyperplasia and glomerulomegaly mediated by increased transforming growth factor-b1 and angiotensin II cause podocyte detachment from the glomerular basement membrane and subsequently glomerulosclerosis.21 These ultimately lead to pathological changes similar to those seen in FSGS and albuminuria, a decline in GFR, and chronic kidney disease progression (Figure 1).

Figure 1. Pathophysiological changes after unilateral native nephrectomy. ERPF, effective renal plasma flow; FSGS, focal segmental glomerulosclerosis.

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References

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18. Hauser P, Kainz A, Perco P, et al. Transcriptional response in the unaffected kidney after contralateral hydronephrosis or nephrectomy. Kidney Int. 2005;68:2497–2507.

19. Kalantar-Zadeh K, Fouque D. Nutritional management of chronic kidney disease. N Engl J Med. 2017;377:1765–1776.

20. Ko GJ, Obi Y, Tortorici AR, et al. Dietary protein intake and chronic kidney disease. Curr Opin Clin Nutr Metab Care. 2017;20:77–85.

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