Caring for adolescent renal patients - Kidney International

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http://www.kidney-international.org & 2010 International Society of Nephrology

Caring for adolescent renal patients Ulf H. Beier1,2, Cynthia Green1 and Kevin E. Meyers1,2 1 2

Division of Nephrology, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA and University of Pennsylvania, Philadelphia, Pennsylvania, USA

Adolescent patients who require the care of a nephrologist present with a variety of challenges. For the treating physician, it is important to be competent in relevant principles of adolescent physiology, such as somatic growth and puberty. It is also essential to be familiar with the stages of adolescent emotional and intellectual development, and their influence on behavior and adherence. Patients transitioning from pediatric nephrology may experience difficulties adjusting to the adult care system. Although the renal pathology of adolescents has more in common with that of adults than that of prepubertal children, there are unique epidemiological, diagnostic, and treatment approaches to these patients that should be considered. Membranous glomerulonephritis and diabetic nephropathy are rare in adolescents, whereas IgA and systemic lupus erythematosus are often important differential diagnoses. Despite all of the challenges posed by adolescents, there is a real prospect of intervening early in the course of chronic kidney disease with the potential to alleviate long-term morbidity. Kidney International (2010) 77, 285–291; doi:10.1038/ki.2009.462; published online 9 December 2009 KEYWORDS: adolescents; chronic kidney disease; glomerulonephritis; nonadherence

When adolescent patients are referred to a nephrologist, multiple issues may interfere with the provision of appropriate medical care, both for physicians and patients alike. Peter et al.1 reported in a survey among internists that, aside from the need for explicit pediatric expertise regarding congenital and childhood-onset conditions, a variety of psychosocial problems were seen as barriers to care, such as the degree of family involvement, patient maturity, and developmental concerns, as well as obtaining financial support to care for patients with complex conditions. Adolescents transitioning from pediatric to adult nephrology and their parents may feel lost in the new autonomous and efficiency-driven environment of adult care.2 Not uncommonly, transition of care can meet with resistance from both patients and parents, manifesting in missed appointments and failure to follow through with care instructions. Adolescents with new onset of renal conditions can be similarly predisposed to nonadherence, lack of followup, and, ultimately, higher morbidity. At the same time, early presentation offers many opportunities for the clinician, particularly the prevention of long-term sequelae of chronic renal disease and its treatment. In the following review, we discuss both the unique challenges and specific opportunities of caring for adolescent nephrology patients. PHYSIOLOGY OF ADOLESCENCE

Correspondence: Kevin E. Meyers, Division of Nephrology, Department of Pediatrics, The Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA. E-mail: [email protected] Received 30 June 2009; revised 23 September 2009; accepted 29 September 2009; published online 9 December 2009 Kidney International (2010) 77, 285–291

Pubescent adolescents experience major physiological, cognitive, and psychosocial changes. These include a somatic growth spurt, the onset of reproductive capacity, appearance of secondary sexual characteristics, as well as important steps in intellectual and psychosocial development. The principal endocrine mechanism driving this process is the neuroendocrine gonadotropin–gonadal axis. In addition to the visible changes of puberty, nearly every organ system undergoes a process of mainly gender-specific maturation, which has important implications for the course of renal disease, its treatment, and disease prevention (Figure 1). It is well known that with the onset of puberty, males have elevated blood pressures as compared with age-matched females, and are more likely to develop hypertension.3 This relationship reverses after menopause. Among the proposed mechanisms to explain this observation are a testosterone-dependent increase in renin activity and direct tubular effects of testosterone such as increased expression of the ENaC channel.3,4 Estrogens, on the other hand, can decrease blood 285

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UH Beier et al.: Adolescent renal patients

GHRH GH

Cardiovascular system

GnRH

Increase in blood pressure (especially in males) Activation of the RAS by testosterone Estrogen protective against hypertension via endothelial NO release and other mechanisms

LH, FSH

Adrenal glands Increased secretion of adrenal androgens Obesity may predispose to premature adrenarche

Kidneys Increased activation of TGF-β, more vulnerable to renal disease processes Males are more susceptible to renal disease Protective effects of estrogen?

IGF-I

Estrogen

Testosterone

Bones Increased mineralization Important to acquire optimum peak bone mass Estrogen inhibits bone reabsorption

Figure 1 | Puberty and the kidney. Follicle-stimulating hormone (FSH), growth hormone (GH), growth hormone releasing hormone (GHRH), gonadotropin-releasing hormone (GnRH), insulin-like growth factor-I (IGF-I), luteinizing hormone (LH), nitric oxide (NO), renin–angiotensin system (RAS), transforming growth factor-b (TGF-b).

pressure by attenuating smooth muscle constriction, both through nitric oxide release as well as endotheliumindependent mechanisms.5 In addition to hypertension, several chronic renal diseases seem to progress faster in males.3 Estrogen reverses numerous profibrotic effects of transforming growth factor-b, such as increased type IV collagen synthesis, whereas testosterone increases proliferation of mesangial cells and stimulates collagen synthesis.3,6 Other hormonal changes of puberty, such as growth hormone and insulin-like growth factor-I release, have the potential to accelerate renal disease through transforming growth factor-b activation, as evaluated for diabetic nephropathy.7 Somatic growth is mediated by the growth hormone–insulin-like growth factor-I axis. In adolescents with chronic renal failure, the response to these growth signals is blunted, especially at the insulin-like growth factor-I level.8 ADHERENCE

As with somatic growth and maturation, intellectual and psychosocial skills undergo equally profound changes during adolescence. Physicians must take each adolescent’s stage of development in these areas into account when formulating an approach to a medical problem, especially with respect to the patient’s understanding of and adherence to medical instructions (Figure 2). Nonadherence is a very common and complex phenomenon among adolescents with chronic diseases. It can manifest as failure to fill prescriptions, delay, 286

or omission of doses, failure to follow through with medical advice, and poor attendance at appointments. There are a variety of reasons for adolescent nonadherence, one of the most important being their limited degree of insight into renal disease and their unwillingness to accept the implications of their condition. Both are dependent on intellectual and emotional maturity.2 Future-oriented and complex abstract thinking usually emerges only during late adolescence and early adulthood. These abilities are critical in adopting behaviors that support the successful management of a chronic disease that requires adherence to a treatment regimen. Mid-adolescence, on the other hand, is characterized by susceptibility to peer pressure, defiance of authority, risk-taking behavior, feelings of invulnerability, and the tendency to revert to concrete rather than abstract thinking in stressful situations, all of which interfere with adherence.9 As rates of development differ among individuals, it can be very challenging to accurately assess a given patient’s level of maturity, especially when advanced social interaction skills and the desire to give pleasing answers may be deceiving. In pediatric nephrology, the issue of nonadherence is most studied in the setting of renal transplantation, with nonadherence to immunosuppressive medications being the single most common cause of renal graft rejection and failure, especially in adolescents.10 Our center has dedicated a major effort to reducing nonadherence in the adolescent transplant population. Kidney International (2010) 77, 285–291

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Early adolescence

Mid adolescence

Concrete thinking

Late adolescence

Abstract thinking

‘I have to take three pills tonight.’

Regression under stress

‘I need this medication to lower my blood pressure.’

Reward oriented

Early long term

Maturing long term

‘I don’t want to take medications because it makes me sick.’

‘Not taking my medicine is bad, but I really don’t like needles.’

‘I don’t like the side effects but I don’t want to lose my graft.’

High emotions

Feeling indestructible

Ideology

Increased emotional reactions, acting on impulse

Difficulties internalizing chronic medical disease

May be susceptible to certain ideas, but intolerant to other points of view

Parent separation

Peer pressure

More independent

Gradual beginning of emotional separation from parents

Very concerned about opinion of peers, body image

Peer pressure less important. Body image concerns may remain.

non-specific ‘yes,’ whereas ‘How many times have you missed your prednisone in the past week?’ will yield a concrete number. Checking on the status of pharmacy refills and asking patients to bring medication bottles to appointments for pill counts can also be useful. More objective measures can provide additional information to help clinicians identify nonadherence in an individual patient, gauge its severity, understand factors influencing level of adherence, and devise interventions that lead to improvement. Biomedical markers allow a nephrologist to rate adherence based on drug assays that quantify serum levels of medications and compare them with results expected if a patient were adherent to the prescribed regimen. However, it is important to note that drug levels suggestive of nonadherence may be influenced by medical complications, just as subjective reporting can be skewed by socially desired answers. For example, decreased dietary intake during a viral illness can increase the absorption of tacrolimus and produce higher drug levels. Simons et al.12 recently published a reporting system combining both biomedical markers as well as subjective reporting. The treating physician needs to combine all available sources of information to arrive at the most accurate assessment of a patient’s adherence status. Intervention strategies

Figure 2 | Adolescent cognitive and psychosocial development. Upper panel—cognitive development; lower panel—psychosocial development. The age range for each phase may vary; in particular, with chronic diseases, significant delay may occur. To control the problem of medical adherence, it is important to adjust to the cognitive abilities and behavioral patterns of adolescents. Adapted from Bell et al.9

Assessment of adherence

The first step in addressing nonadherence is accurately determining a patient’s adherence status of a patient. Before surgery, each patient and family are evaluated by a psychologist and a social worker who can screen and identify risk factors for nonadherence. Our center has developed a standardized protocol for conducting these evaluations.11 It is important to realize that self-reports by patients and family members tend to overestimate adherence levels. However, accuracy can be increased by using semi-structured interviewing, such as the Medical Adherence Measure, which assesses a patient’s knowledge of prescribed regimens, actual behavior, obstacles to adherence, organizational skills, and level of family support. The way a question is framed can influence the accuracy of the answer received. Asking ‘Do you take all your medications?’ frequently generates a Kidney International (2010) 77, 285–291

Once nonadherence is confirmed, interventions to improve adherence should be tailored to the individual patient and family situation. Education regarding the nature of the disease and the relationship between a prescribed regimen and the medical outcome, including the negative effects of nonadherence, can be helpful for patients who lack understanding. It is important to ensure that the information is delivered in a manner appropriate to the patient’s developmental and cognitive status—pictures, charts, and simple language can be helpful for younger or less mature patients— and is repeated on multiple occasions. Practical recommendations can also be beneficial with regard to organizing medication administration, such as using a weekly pill box and keeping medications in a single, convenient location. Streamlining medication regimens, by reducing the overall number of medications or adjusting dosage times or forms (pills versus liquids), can also help, as more complex regimens have been associated with nonadherence. Behavioral strategies can be offered, such as using reminders in the form of notes posted in the home, watch alarms, or calendars. Psychosocial factors must also be considered when nonadherence becomes a problem. Patients who are depressed or anxious, who have psychological issues such as attention deficit disorder, or whose families are stressed, conflictual, or otherwise poorly functioning, should be referred for mental health services. Table 1 provides a summary of the main points from our center’s experience.13 We would encourage adult nephrologists working with adolescent patients to keep parents involved, as it is probably one of the most effective measures available to physicians trying to maintain adherence. 287

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Table 1 | Top 10 suggestions for enhancing adolescent adherence 1. 2. 3. 4. 5. 6. 7. 8.

Maintain an open and honest partnership. Establish small, realistic goals. Provide a range of acceptable options from which to choose. Consider the patient and the family’s daily schedule and routine. Give simple and concise prescriptions. Deliver instructions in a clear, explicit form and repeat them. Evaluate the patient’s understanding and recollection of instructions. Use gradual implementation of complex regimens in small, manageable steps. 9. Identify reminders in patient’s environment. 10. Involve all systems (family, psychosocial experts, school personnel). Adapted from Zelikovsky and Walsh.13

Transitioning care

Transition of medical care from a pediatric to an adult nephrologist can, at times, be difficult. Not uncommonly, patients will miss scheduled appointments with their adult providers or try to return to pediatric care (for example, by presenting to the emergency room of their pediatric hospital). In our experience, parents also have difficulties during the transition. Parents frequently are reluctant to push chronically ill children toward a more age-appropriate level of independence, influenced by feelings of guilt or a fear that the youngster will not be able to manage his or her own health care needs. In addition, transitioning to an adult nephrologist can make parents feel powerless, out of control, and excluded. They are, by law, not entitled to freely access confidential medical information once their children reach the age of majority, and the unwieldy process of gaining consent to receive firsthand explanations from the patient’s physician does not easily fit into the fast-paced and efficiency-driven operation of adult medical care. At the same time, the autonomy-centered adult medical environment can make adolescent adherence problems much more difficult to address, especially if more invasive control mechanisms become warranted. The subject of transitioning from pediatric to adult medical providers has been reviewed by Bell et al.9 and other authors. We would like to add that in our experience, extending the involvement of parents into young adulthood, while gradually shifting the responsibility to the patient, should be considered. This will not only encourage the parents’ cooperation with transitioning but also use them as vital tools in addressing the significant challenge of adolescent nonadherence. RENAL PATHOLOGY OF ADOLESCENCE

Adolescent patients usually are referred with findings of macro- or microscopic hematuria, along with proteinuria, hypertension, edema, or impaired renal function. Although the spectrum of underlying renal pathology is not very different from that of young adults,14 it is important to realize the differences that do exist and their implications. IgA nephropathy

IgA nephropathy can affect all ages; however, it has a peak incidence in the second and third decades of life. It is 288


remarkable for its very wide range of presenting clinical features and variable disease progression after diagnosis. Important risk factors for progression to end-stage renal disease (ESRD) include an elevated creatinine, proteinuria 41 g/day, and hypertension.15 Young age has been shown by multiple investigators to be a good prognostic marker regarding the risk of developing ESRD, whereas older age is an independent adverse risk factor.16 Acute poststreptococcal glomerulonephritis

Acute poststreptococcal glomerulonephritis has changed its epidemiological pattern over the years. A study by Ilyas and Tolaymat17 reported that pharyngitis has replaced impetigo as the predominant cause of acute poststreptococcal glomerulonephritis, and that the median age has risen from 4.25 to 7 years, with an increasing number of cases presenting as adolescents and adults. The overall prognosis for recovery from acute poststreptococcal glomerulonephritis in children and adolescents remains excellent. Rapidly progressive glomerulonephritis

Rapidly progressive glomerulonephritis (RPGN) is a severe form, usually defined by more than 50% of the glomeruli showing crescent formation.18 If left untreated, RPGN may lead to renal failure within a few weeks or months. Although RPGN can, in principle, arise from any inflammatory glomerulonephritis, it is very commonly caused by antineutrophil cytoplasmic autoantibodies-mediated glomerulonephritis, particularly in the elderly. In adolescents, it may be seen in IgA nephropathy, Henoch–Scho¨nlein purpura, membranoproliferative glomerulonephritis, systemic lupus erythematosus, and other causes of nephritis.14 Given the grave prognosis of RPGN, many pediatric nephrologists will initiate treatment even if renal biopsy reveals less than 50% glomerular involvement. Membranoproliferative glomerulonephritis

Membranoproliferative glomerulonephritis can occur in all ages, with a peak incidence in adolescence and young adulthood, and is an important cause of ESRD in the pediatric population. The idiopathic form predominates in younger patients, whereas secondary membranoproliferative glomerulonephritis is more common in adults.19 An important difference is the approach to treatment. Unlike adult patients, children and adolescents with membranoproliferative glomerulonephritis associated with nephritic-range proteinuria may benefit from corticosteroid administration. In the International Study of Kidney Disease in Children, alternate-day prednisone was administered for 130 months, and 61% of the treatment group had stable renal function at the end of the study period, as compared with 12% of the controls.20 However, there is a paucity of randomized controlled trial data available, predating the now routine use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for renoprotection. Kidney International (2010) 77, 285–291


Alport syndrome

Alport syndrome, the most common form of hereditary nephritis, is a function of impaired production or assembly of the type IV collagen network, resulting in hematuria, proteinuria, and progressive chronic kidney disease (CKD). Bilateral sensorineural hearing loss and ocular defects are commonly found. The diagnosis is frequently established by biopsy, after patients present with hematuria and/or proteinuria and a family history of hereditary nephritis. The differential diagnosis of thin glomerular basement membrane nephropathy is, in some cases, not easily distinguished, as these patients are frequently heterozygous carriers for autosomal recessive Alport syndrome.21 Alport syndrome is associated with different gene mutations. In the more common X-linked variant, the a-5 chain of collagen IV (COL4A5) is affected. The autosomal forms are linked to genes encoding for COL4A3 and COL4A4. Progression to ESRD usually occurs in adulthood, but may arise during adolescence. In the X-linked form, affected female adolescents will usually have only microscopic hematuria with or without proteinuria secondary to X-chromosomal lyonization. Progression to ESRD is uncommonly reported in female adolescents.22 Autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) can be recognized from fetal life to adulthood. ADPKD is a systemic disease, with cysts occurring in the kidneys, liver, pancreas, and other organs, including aneurysms of the vasculature. In contrast to autosomal recessive polycystic kidney disease, liver involvement is predominantly cystic and hepatic failure is rare. Extrarenal manifestations of ADPKD are uncommon in children and adolescents. Adolescents with ADPKD may present with flank pain, hematuria, renal colic, urinary tract infections, or hypertension, but they may be asymptomatic. On imaging, multiple renal parenchymal cysts are generally visible, and usually increase in size and number with age. In general, the combination of a parent with ADPKD and more than one cyst in a child is considered diagnostic for ADPKD. Treatment is largely according to symptoms. However, diagnosis of urinary tract infections can be challenging, as the infection may be contained within a cyst, not producing diagnostic pyuria. Furthermore, traditional pediatric first-line antibiotics, such as cephalosporins, may be ineffective because of poor cyst penetration. A sulfonamide or fluoroquinolone is usually preferred. Screening for extrarenal manifestations, such as intracranial aneurysms, is not routinely recommended in children, and magnetic resonance angiography is usually reserved for symptomatic patients or those with a strong family history of cerebrovascular disease.23 Nephrotic syndrome

Minimal change disease is highly prevalent in pediatric-onset nephrotic syndrome, especially in prepubertal children, when compared with that arising in adults. Although a variety of Kidney International (2010) 77, 285–291

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authors have observed an increased prevalence of focal segmental glomerulosclerosis in recent decades,24 treatment patterns have remained consistent, including a consensus that classic steroid-responsive minimal change nephrotic syndrome does not warrant an initial biopsy. This does not apply to postpubertal patients, given the increased incidence of focal segmental glomerulosclerosis in adolescence. Furthermore, a careful consideration of secondary causes of nephrotic syndrome, such as malignancy, is advised. Membranous glomerulonephritis is uncommon in children and adolescents, accounting for only 3% of pediatric nephrotic syndrome.25 It is usually seen in the context of class V systemic lupus nephritis.26 Importantly, children and adolescents may present with membranous lupus in the absence of extrarenal manifestations of lupus disease. Renal manifestations of sexually transmitted diseases

Sexually transmitted diseases and their treatment may affect the kidney. Infections may be transmitted vertically (congenitally) or horizontally. The three infections that may lead to nephropathy include human immunodeficiency virus, hepatitis B, and hepatitis C.27 One of the earliest signs may be proteinuria. These diagnoses should be considered in adolescent patients with sexual risk-taking behavior. Although focal segmental glomerulosclerosis is the most common HIV-associated nephropathy, other presentations are possible, including minimal change disease, IgA, or a lupus-like nephropathy.27 Renal replacement therapy through dialysis and renal transplantation is possible and may prolong life expectancy. HYPERTENSION AND OTHER CARDIOVASCULAR RISK FACTORS

Hypertension in young adults is a known risk factor for left ventricular hypertrophy and coronary artery disease.28 Adolescents with stage II hypertension are at increased risk of developing hypertensive encephalopathy, seizures, cerebrovascular accidents, and congestive heart failure. On the basis of these observations, early detection and intervention in children with hypertension is beneficial in preventing long-term complications. Early intervention has significant preventive potential, reducing the future burden of adult cardiovascular disease. Current recommendations for diagnosis, evaluation, and treatment of childhood hypertension are provided by the fourth report of the National High Blood Pressure Education Program (NHBPEP) Working Group on High Blood Pressure in Children and Adolescents.29 In children and adolescents, unlike adults, secondary hypertension is common and may arise because of a variety of conditions, such as renal parenchymal or vascular disease. Given the young age of the patients, it is necessary to consider alternative causes, such as a previously undiagnosed coarctation of the aorta. A very common reason for adolescent referral is so-called ‘white coat hypertension,’ whose accurate diagnosis largely depends on a detailed history and age-appropriate physical exam. If initial screening suggests 289

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this diagnosis, ambulatory blood pressure monitoring is recommended.30 To treat hypertension, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are frequently used. With regard to adolescents, it is important to consider issues of nonadherence and teen pregnancy (and the need to stop any angiotensin-converting enzyme inhibitor use), as well as the possibility of prerenal azotemia in patients who are at risk for dehydration, such as from strenuous exercise.14 Although hypertension is prevalent and important, it alone cannot explain the increased incidence of adult CKD, which has risen from 10 to 13.1%. Other important factors include increasingly prevalent obesity and diabetes mellitus.31 The Young Finns Study documented that early exposure to cardiovascular risk factors may induce changes in arteries that contribute to the development of atherosclerosis.32 Childhood obesity, a key risk factor in developing these conditions, has become a major public health concern. After a continued increase in prevalence in both adults and children during the past decades, childhood obesity has stabilized at 23% in African Americans and Mexican Americans and at 12% in Caucasians.33 Given the grave implications of obesity for renal disease and the benefits of weight reduction, it is important that these problems be addressed during office visits. RENAL REPLACEMENT THERAPY Management of CKD

There are a number of important differences in the management of CKD in adolescents compared with adults. Foremost, somatic growth is a central concern. Treatable causes of growth retardation in adolescents include renal osteodystrophy, metabolic acidosis, inadequate nutritional intake, disturbances in the growth hormone–insulin-like growth factor-I axis, and chronic treatment with steroid medications.34 Bone health in adolescents can present special challenges, in particular, the unwillingness of many adolescent patients to comply with a phosphorus-restricted diet. This may result from both peer pressure and limited understanding of the long-term implications of nonadherence. To maximize somatic growth potential, protein intake is not restricted and is maintained at the recommended daily allowance.35 In addition, recombinant human growth hormone is widely used. In a meta-analysis by Vimalachandra et al.,36 which evaluated 15 randomized controlled trials involving 629 children, 28 IU/m2/week of recombinant human growth hormone produced a 3.8 cm yearly height increase compared with untreated patients. The response to treatment is, however, impaired in patients on dialysis or with severely delayed puberty. In addition, there are a variety of obstacles to children and adolescents actually receiving daily recombinant human growth hormone injections, including patient resistance, parental refusal, and secondary hyperparathyroidism. Peritoneal dialysis versus hemodialysis

From a purely medical perspective, there are many convincing arguments in favor of peritoneal dialysis (PD) as 290


opposed to hemodialysis (HD). In the short term, PD has been shown to be associated with superior outcomes compared with HD.37 Furthermore, PD allows preservation of vascular access, which is of particular importance to young patients facing a lifetime of renal replacement therapy. Children and adolescents on HD accumulate risk factors leading to early and progressive coronary artery calcifications.38 In addition, nighttime administration of PD allows children to attend school more regularly, and self-care permits more flexibility with vacations and travel. Nevertheless, decisions regarding preferred dialysis modality for any individual patient must take into account additional considerations. Adolescents may find the prolonged treatment time of nocturnal PD too intrusive into their social time, leading to skipped or shortened treatments and poor outcome from nonadherence. In addition, not all families have the time, resources, or appropriate home setting to support successful PD. Our center, in accordance with Centers for Medicare & Medicaid Services requirements, sends a social worker and a dialysis nurse on home visits to carefully evaluate hygienic and psychosocial factors before initiation of PD. If HD is indicated, it is important to consider early placement of an arteriovenous fistula.37 For young patients, this can be complicated by the paucity of pediatric vascular surgeons. In a select subgroup of patients, nocturnal HD may be suitable. Transplantation

Since 1963, when Willard Goodwin first used corticosteroids to achieve immunosuppression in renal allograft patients, this medication has maintained a valuable role in organ transplantation. However, the wide range of side effects is substantial. Particularly in children and adolescents, growth retardation, cushingoid features, and hyperlipidemia are of concern and may lead to co-morbidities and nonadherence. With the emergence of cyclosporine, followed by tacrolimus, mycophenolate mofetil, and sirolimus, hope arose that the role of steroids could be reduced. Although initial steroidsparing protocols resulted in increased rejection rates, more recent trials using T-cell-depleting antibodies at induction have been associated with little or no increase in rejection rates and no difference in graft survival versus maintenance prednisone, both in randomized and nonrandomized trials at 5–7-year follow-up.39 However, other immunosuppressive agents can also have substantial side effects. Calcineurin inhibitors are well known for their nephrotoxicity, making the recipient susceptible to infections such as BK virus and predisposing to malignancies. Apart from posttransplant lymphoproliferative disorder, the high risk of skin cancer is of particular concern, particularly in adolescent patients concerned with body image. Consequentially, several groups have developed protocols to minimize exposure to immunosuppressive agents. At our center, we have participated in a calcineurin inhibitor-free regimen based on Campath-1H (monoclonal anti-CD52 antibody),40 and in steroid withdrawal and avoidance protocols. Kidney International (2010) 77, 285–291

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CONCLUSION

Although adolescent and adult nephrology patients are similar in many ways, several prominent differences are noted. First and foremost, it is important for the nephrologist to recognize adolescent developmental stages and their influence on behavior and adherence. Adherence is probably the most profound problem that physicians have to address in any adolescent patient with renal disease, and should be a major focus of future research. Second, the epidemiology of glomerular pathology is slightly different. Membranous glomerulonephritis and diabetic nephropathy are rare, whereas acute poststreptococcal glomerulonephritis, IgA nephropathy, and Henoch-Scho¨nlein purpura are important differential diagnoses to consider in adolescents. Third, the physiology of the adolescent impacts the direction of treatment on several levels, whether considering the implications of somatic growth in choosing to use growth hormone or steroid-sparing regimens posttransplantation or calculating the likelihood of teen pregnancy before prescribing an angiotensin-converting enzyme inhibitor. Finally, working with adolescents provides an important and rewarding opportunity for early intervention in the course of CKD, with the potential to alleviate long-term morbidity.

16. 17.

18. 19. 20.

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26.

DISCLOSURE

All the authors declared no competing interests.

27.

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