and Mikolaj Przydacz1
(1)
Department of Urology, Jewish General Hospital, McGill University, Montreal, QC, Canada
Keywords
Chronic kidney diseaseEnd-stage kidney diseaseAcute kidney injuryCreatinine clearanceCystatin CUrinary diversionRenal replacement therapyIntroduction
The ultimate consequence of all upper urinary tract complications in neurogenic patients is the impairment of renal function. Despite the improvement of bladder management strategies in recent years, renal failure remains a significant cause of morbidity in this specific population. Renal failure represents a significant late consequence of neurogenic bladder dysfunction. Acute/chronic abnormalities contributing to renal insufficiency in neurologically impaired patients include [1–5]:
General/urological abnormalities:
pyelonephritis and other infections (in particular recurrent and chronic)
renal stone formation
hydronephrosis (with or without upper urinary tract obstruction)
vesicoureteral reflux
complete neurogenic lesions
quadriplegic dysfunctions
high spinal lesions
indwelling catheterization
aggressive treatment methods aiming to increase urethral resistance without management of bladder pressure
bladder-emptying techniques with increase of bladder/abdominal pressures (e.g., Valsalva or Crede maneuvers)
Urodynamic abnormalities:
high storage pressure (>40 cm H2O)
high voiding pressure (>90 cm H2O)
sustained high-pressure detrusor contractions
duration of detrusor overactivity (longer than one-third of the duration of cystometry)
decreased bladder compliance (<10 cm H2O)
reduced bladder capacity
detrusor-sphincter dyssynergia
high post-void residual (>30% of bladder capacity)
Epidemiology
Individuals with neurogenic lower urinary tract dysfunction are at higher risk of renal deterioration compared to the general population. However, current epidemiological data are strongly limited. The majority of studies insufficiently analyzed the severity and duration of the underlying neurological disease or did not perform specific subgroup analyses. It is agreed that the risk of renal dysfunction increases with the time and progression of the underlying disease. The greater the impairment with underlying neurological disorder, the greater the risk of upper tract deterioration. It has been estimated that the rate ratio of renal failure compared with the general population for neurogenic patients ranges between 0.4 and 11.5 [6]. Those after spinal cord injury (in particular with suprasacral lesions) and neural tube defects were found to have a substantially increased risk of renal insufficiency. One-third of these individuals will develop some degree of renal deterioration over time [7–10]. On the other hand, the occurrence of renal insufficiency secondary to neurogenic bladder dysfunction in patients with multiple sclerosis is not particularly common and close to that in the general population [6, 11]. Epidemiological data of end-stage renal disease in other neurological conditions are sparse. It is worth pointing out that during past decades renal failure was the leading cause of death in neurogenic patients, particularly in those after spinal cord injury [12, 13]. Improvements in follow-up monitoring, bladder management strategies, and treatment of complications have virtually eliminated neurogenic bladder-related mortality in developed countries and have significantly contributed to increase the lifespan of these patients [14]. The leading causes of death in neurogenic patients are now reported to be pneumonia/influenza, septicemia, cancer, ischemic heart disease, and suicide [15].
Diagnosis
Renal deterioration is typically diagnosed during routine follow-up of asymptomatic neurogenic individuals (chronic kidney disease). This condition is a consequence of poorly managed neurogenic bladder and/or chronically developing complications. Renal failure might also be diagnosed as a result of acute clinical conditions requiring further investigation (acute kidney injury). The diagnosis in both cases is primarily laboratory-based.
Chronic Kidney Disease (Chronic Renal Failure)
Definitions and Staging
The Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation and the Kidney Disease Improving Global Outcomes (international guideline group) have developed definitions, classifications and guidelines of chronic kidney disease (CKD) [16]. The guidelines define CKD as abnormalities of kidney function or structure, present for >3 months, with implications for health. Criteria for CKD include:
Decreased glomerular filtration rate (GFR) (for >3 months)
GFR <60 mL/min per 1.73 m2
Markers of kidney damage (≥1 for >3 months)
albuminuria (albumin excretion rate ≥30 mg/24 h or albumin-creatinine ratio ≥30 mg/g)
urine sediment abnormalities
electrolyte and other abnormalities due to tubular disorders
histological abnormalities
structural abnormalities detected by imaging
history of kidney transplantation
It was also emphasized that in patients with or suspected of CKD, chronic renal failure or renal function should be classified with GFR and albuminuria categories as they most reliably express the level of severity:
GFR category
stage 1—kidney damage with normal or increased GFR (>90 mL/min/1.73 m2)
stage 2—mild reduction in GFR (60–89 mL/min/1.73 m2)
stage 3a—moderate reduction in GFR (45–59 mL/min/1.73 m2)
stage 3b—moderate reduction in GFR (30–44 mL/min/1.73 m2)
stage 4—severe reduction in GFR (15–29 mL/min/1.73 m2)
stage 5—kidney failure (GFR <15 mL/min/1.73 m2 or dialysis)
Albuminuria category
stage 1—normal to mildly increased (albumin excretion rate <30 mg/24 h or albumin-creatinine ratio <30 mg/g)
stage 2—moderately increased (albumin excretion rate 30–300 mg/24 h or albumin-creatinine ratio 30–300 mg/g)
stage 3—severely increased (albumin excretion rate >300 mg/24 h or albumin-creatinine ratio >300 mg/g)
It should be noted that in the absence of evidence of kidney damage, neither G1 nor G2 GFR categories alone fulfill the criteria for CKD. It has been proposed that GFR and albuminuria levels should be used together, rather than separately, to improve prognostic accuracy in the assessment of CKD. This combined evaluation should be performed particularly in risk assessment for overall mortality, cardiovascular disease, end-stage kidney failure, acute kidney injury, and the progression of CKD. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has been recommended for reporting estimated GFR, because of having less bias than the MDRD equation [17].
Signs and Symptoms
CKD may remain asymptomatic and clinically silent for a long time. Clinical manifestations typically appear in stages 4–5 of GFR (<30 mL/min/1.73 m2) when metabolic/endocrine disturbances with fluid/electrolyte imbalances become apparent. The majority of symptoms are non-specific, wide ranging, and gradual in onset. Possible signs and symptoms include but are not limited to [18]:
Malnutrition
Anorexia
Body mass loss
Reduced exercise capacity
Weakness
Fatigue
Sleep disturbances
Impaired cognitive and immune function
Peripheral edema
Pulmonary edema
Hypertension
Heart failure
Anemia
Evaluation of patients with renal deterioration should also include assessment of current medications, both prescribed and over-the-counter, as these may precipitate or worsen kidney dysfunction . These agents include, but are not limited to: blockers of the renin-angiotensin-aldosterone system (including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, aldosterone inhibitors, direct renin inhibitors); diuretics; nonsteroidal anti-inflammatory drugs; metformin; lithium; calcineurin inhibitors; digoxin; and herbal remedies [19].
Laboratory Data
Laboratory testing should include: complete blood count; basic metabolic panel (creatinine, blood urea nitrogen (BUN), bicarbonate, electrolytes, serum pH); urinalysis (urine pH, gravity, osmolarity, albumin concentration); serum albumin levels; and lipid profile. However, data for neurogenic patients, in particular for those after spinal cord injury, suggest that the creatinine clearance based on serum creatinine levels has little value as a screening measure for renal disease in this population because of its variability in serial testing [20–22]. Muscle denervation, muscle disuse, decreased muscle mass (muscle atrophy), body habitus, as well as type and chronicity of dysfunction/injury substantially contribute to lower creatinine production, with resultant lower serum creatinine measurements [23]. Therefore, it is highly possible that neurogenic patients with a serum creatinine and creatinine-based GFR in the normative range may have severely impaired renal function. Renal function evaluation by serum creatinine-based equations is biased, and renal function of neurogenic patients is thus potentially systematically overestimated. Concurrent findings have been demonstrated for the estimation of creatinine clearance with the 24-h urine collection [20, 24]. Urine collection may be additionally impaired by incomplete collection of all urine produced during 24 h (especially in incontinent patients), inaccurate measurement of urine volume, and variability of the laboratory test for urinary creatinine concentration. Moreover, a complete 24-h urine collection often requires a well-informed patient and adequate staff support, thereby limiting the utility of the test. Inaccurate assessment of renal function may delay medical and urological management aiming to protect the upper urinary tract. In view of these findings, it has been proposed to not rely on serum creatinine and estimated GFR in isolation for monitoring renal function in people with neurogenic lower urinary tract dysfunction [25].
When an accurate measurement of GFR is required (e.g., in patients with acute decrease in renal function or if imaging of the kidneys suggests that renal function might be compromised), isotopic GFR with radionuclide scans should be considered [21, 25]. Nonetheless, because this test is time-consuming, labor-intensive, and expensive, it may be impractical for routine use. Therefore, another method of renal assessment that should be considered in the neurogenic population and in patients with muscle-wasting conditions involves the measurement of serum cystatin C [26, 27]. If cystatin C is measured, it has been recommended to use a GFR estimating equation to derive GFR from serum cystatin C rather than relying on the serum cystatin C concentration alone [19]. The CKD-EPI cystatin C equation has been shown to be the most precise in estimating cystatin C-based renal function in patients with neurogenic bladder [24]. Studies have demonstrated that in neurogenic patients the cystatin C-estimated GFR is a better screening test for early renal insufficiency that is not detected by creatinine-based calculations [28–30]. It should be considered particularly in individuals with creatinine-estimated GFR between 45 and 59 mL/min/1.73 m2 who do not have markers of kidney damage and may suffer from silent clinical deterioration of kidney function [19]. Of note, physicians should bear in mind that cystatin C and creatinine-based GFR are insensitive in detecting unilateral renal damage [26]. Unilateral kidney damage still requires nuclear medicine scans.
Imaging Studies
Imaging studies that can be used in the diagnosis of CKD include renal ultrasound, computed tomography, magnetic resonance imaging, renal radionuclide scanning (renal scintigraphy), intravenous urography, and retrograde pyelography. The use of a specific imaging technique depends on the clinical scenario and any developed complications of neurogenic bladder. Small contracted kidneys are typical imaging findings in those with end-stage renal disease (Fig. 13.1) [31].
Fig. 13.1
End-stage renal disease . Nonenhanced CT shows small contracted both kidneys and prominent fatty tissues in the renal sinus and perirenal space (with permission from Kim and Kim [31])
Acute Kidney Injury
Definitions and Staging
Acute kidney injury (AKI), previously termed acute renal failure, is an abrupt or rapid decline in renal filtration function [32]. AKI has been defined as any of the following [19]:
Increase in serum creatinine by ≥0.3 mg/dL (≥26.5 μmol/L) within 48 h
Increase in serum creatinine of 50% or greater (1.5-fold from baseline), which is known or presumed to have occurred within the prior 7 days
Urine volume <0.5 mL/kg/h for 6 h
AKI is classified as prerenal, intrinsic, and postrenal. In daily clinical practice of neurourological patients, clinicians may encounter those with intrinsic and postrenal causes. The first group includes inflammatory insults to the kidney (pyelonephritis) and the second group encompasses obstruction to the passage of urine (stone disease). Furthermore, AKI may develop as a breakdown of CKD, and some recommend that all persons with CKD are considered to be at increased risk of AKI [19]. AKI is staged for severity according to the certain criteria detailed in Table 13.1 [29].
Table 13.1
Staging of the severity of acute kidney injury
Stage | Serum creatinine | Urine output |
|---|---|---|
1 | 1.5–1.9 times baseline or ≥0.3 mg/dL (≥26.5 μmol/L) increase | <0.5 mL/kg/h for 6–12 h |
2 | 2.0–2.9 times baseline | <0.5 mL/kg/h for ≥12 h |
3 | 3.0 times baseline or increase in serum creatinine to ≥4.0 mg/dL (≥353.6 μmol/L) or initiation of renal replacement therapy or in patients ≤18 years, decrease in GFR to <35 mL/min per 1.73 m2 | <0.3 mL/kg/h for ≥24 h or anuria for ≥12 h |
For day-to-day clinical practice, AKI can also be classified as oliguric or non-oliguric on the basis of daily urine excretion. Oliguria is defined as a daily urine volume of less than 400 mL and oliguric AKI has a worse prognosis compared to non-oliguric failures. Anuria is defined as a urine output of less than 100 mL/day and, if abrupt in onset, suggests bilateral obstruction or severe injury to both kidneys. Other staging systems (e.g., the RIFLE classification) may be considered [33].
Signs and Symptoms
The main complaints depend on the clinical scenario and underlying cause of AKI. Relevant signs and symptoms of pyelonephritis and urolithiasis have been discussed in Chaps. 10 and 11, respectively. Despite cause-related signs and symptoms, patients may present with abnormalities specific to AKI. These include cardiovascular decompensation with irregular rhythms and blood pressure, pulmonary decompensation with difficult breathing and impaired physical activity, metabolic disturbances with abnormal levels of electrolytes (in particular acidosis and hyperkalemia), and neurological impairment with decreased cognitive function. Nevertheless, due to neurological impairment, the early stages of AKI are usually asymptomatic and the diagnosis is typically based on elevated creatinine levels. It may take 24 h or more for initially normal creatinine levels to show a definitive increase. Similarly to CKD, the patient’s medication list should be carefully reviewed, as many of prescribed and over-the-counter drugs may worsen renal function.
Laboratory Data
Laboratory testing in patients with AKI should include: complete blood count; basic metabolic panel (creatinine, BUN, bicarbonate, electrolytes, serum pH); urinalysis (urine pH, gravity, osmolarity, albuminuria); liver function tests; coagulation tests; and glucose level.
Imaging Studies
As the most common causes of AKI in neurogenic patients are pyelonephritis and stone disease, computed tomography should be a first-line imaging modality for this population. The remaining methods of imaging should be considered when indicated by the clinical scenario.
Treatment
Treatment of Chronic Kidney Disease
The urological care of patients with CKD should focus on delaying or halting the progression of CKD by treatment of the underlying bladder dysfunction. This primarily includes reassessment of bladder management. Preservation or improvement of already deteriorated renal function is achieved through treatment aimed at minimizing the generation of elevated pressure in the lower urinary tract. New urodynamic evolution might sometimes be necessary. Other conditions that contribute to renal dysfunction (e.g., hydronephrosis, stone disease, recurrent urinary tract infections) should be properly treated. Previous chapters covered the treatment of specific bladder dysfunctions and related complications. If low-pressure bladder system cannot be achieved, invasive non-reversible surgery with urinary diversion should be considered. However, in some patients the only treatment options for renal failure are dialysis or renal transplantation.
Urinary Diversion
Urinary diversion, although frequently performed in the past for the treatment of neurogenic lower urinary tract dysfunction, is now required only in special circumstances. This invasive treatment option may be considered for the protection of the upper urinary tract and for the improvement of quality of life in patients with [34, 35]:
Multiple failures of non-invasive and less invasive management methods
Worsening hydronephrosis accompanied by progressive renal deterioration or intractable vesicoureteral reflux due to thick-walled bladder
Recurrent episodes of urosepsis
Persistent storage and emptying failure
Unacceptable incontinence
Inability to perform intermittent catheterization
Complications of indwelling catheterization, including urethral destruction and urethrocutaneous fistulas
Perineal pressure ulcer
Bladder malignancy requiring cystectomy
The selection of urinary diversion procedure is largely based on the surgeon’s experience and opinion, as well as patient’s medical condition. The main considerations are presented in Fig. 13.2 [34].
