Hospital Medicine

IgA Nephritis

Jump to Section

I. What every physician needs to know.

IgA nephropathy (IgAN) is the most common cause of primary (idiopathic) glomerulopathy wordwide, accounting for 10-40% of cases. Peak incidence is in the 2nd and 3rd decade of life, with at least a 2:1 male to female predominance, and occurs with greatest frequency in Asians and Caucasians (very rare in African Americans).

The primary etiology of IgAN remains largely unknown despite wide speculation. Hypotheses include chronic upper respiratory tract infections, dietary antigens (glutean), as well as genetic factors, which may result in increased IgA complex formation.

Like many other glomerulonephritities, IgAN is an immune complex-mediated glomerulonephritis. The primary mechanism in its pathogenesis is the deposition of polymeric IgA complexes (IgA1 subclass) within the renal mesangium that trigger glomerular injury. Factors that lead to increased formation of these IgA complexes are thought to include dysregulated synthesis and metabolism of IgA. It is only when IgA complexes have the propensity for mesangial deposition and subsequent complement (C3) activation leading to cellular injury that one develops what is recognized to be IgA nephritis. In other words, IgA deposits are also seen on kidney biopsies of healthy individuals (estimated at 3-16%) who do not have any evidence of renal injury or IgAN.

The clinical presentation of IgAN varies. The majority of patients present with recurrent gross hematuria, which may follow upper respiratory tract infections. Approximately 30-40% of patients present with asymptomatic microscopic hematuria with or without proteinurea. A minority present with more severe disease characterized by hypertension, decreased GFR, or nephrotic syndrome. While the diagnosis can be suspected based on clinical signs and symptoms, the gold standard is renal biopsy demonstrating pathognomonic IgA immune complex deposition on immunoflourescence microscopy.

The disease course and prognosis is also variable. Approximately 10-15% of patients diagnosed in the early stages of disease undergo spontaneous remission, while 30% of patients have a progressive disease course. In those with progressive disease, ESRD will develop in about 15-20% of patient within 10 years and 30-40% within 20 years of diagnosis. The degree of proteinuria (>0.5g/24h), presence of hypertension, persistant hematuria, and decreased GFR strongly predict a worse renal outcome,especially if these are present on diagnosis. Histological parameters such as mesangial and endocapillary hypercellularity, glomerulosclerosis, and tubular fibrosis also predict worse renal outcomes. The presence of necrosis and crescents (>50%) can have the potential for more rapid deterioration.

There is no cure for IgAN. The goal of treatment is to stop or slow down disease progression. Evidence-based treatment guidelines are lacking due to poor quality studies with small sample size, sub-optimal methodologies, and confounding variables. Management primarily involves addressing the clinical indicators of disease such as proteinuria and blood pressure. Similar to other chronic kidney diseases, patients should be on reno-protective medications such as ACEi/ARBs. In patients noted to have progressive disease, the mainstay of treatment involves corticosteroids, usually for a 6-month period. Other therapies, including tonsillectomy, fish oil, antiplateletes/anticoagulants, and other immunosuppressive have been studied, but no conclusive recommendations can be made due to mixed results.

II. Diagnostic Confirmation: Are you sure your patient has IgA Nephritis?

Although the presence of IgAN may be suspected based on clinical history and laboratory data, its diagnosis can only be confirmed on renal biopsy (gold standard).

The pathognomonic finding on biopsy is the presence of globular IgA deposits in the mesangium and occasionally the glomerular capillary wall on immunofluorescence microscopy. This is often accompanied by C3 and IgG mesangial deposition which signifies concurrent complement activation and injury. The immunofluorescence findings in IgAN are indistinguishable from Henoch-Schonlein purpura.

On light microscopy, one may see mesagnial proliferation to varying degrees as well as matrix expansion. Findings such as crescents formation (more than 50%) and segmental necrosis indicate more severe and rapidly progressing disease. Findings such as glomerular sclerosis and tubulointerstitial fibrosis are consistent with more chronic renal disease and a generally present in patients who present with a decrease in GFR.

On electron microscopy, deposits are primarily noted in the mesangium and to a lesser degree in the subendothelial and subepithelial spaces.

Until recently, there was no international consensus on how to interperate the many different histological findings present on biopsy and their clinical signficiance, specifically in terms of disease severity, progression, and prognosis. In 2009, The International IgA Nephropathy Network and Renal Pathology Society published theOxford Classification system with the goal of developing a universal classification for IgAN that would identify pathological features that have been proven to correlate with clincial outcome, independent of clinical data.

This system (MSET) potentially allows a universal language and standardization in the interpretation of renal biopsy results. This classification was developed by examining the the biopsies of 265 adults and children on initial presentation. Patients were followed for 5 years in order to identify which pathological features have the most prognostic signficance. Validation studies are ongoing to ascertain whether this classification system can be used to predict renal outcomes in IgAN.

The current recommendation based on the Oxford Classification system is that every biopsy of IgA nephropathy include scores based on the presence or absence of the following variables:

  • Mesangial hypercellularity score (M0 or M1)

  • Segmental glomerulosclerosis (S0 or S1)

  • Endocapillary hypercellularity (E0 or E1)

  • Tubular atrophy/interstitial fibrosis (T0, T1, T2)

Of note, biopsies that contain fewer than eight glomeruli cannot be interpreted in the above scoring system for prognostic value. Also, it is important to note that the above classification does not "score" the presence of crescents or segmental necrosis due to sampling size, which are known pathological features that represent more severe disease and portend a poor prognosis.

A comprehensive renal biopsy report a patient with IgAN should include:

  1. Detailed description of the features present on light microscopy, immunohistochemistry and electron microscopy

  2. Summary of the following pathologic features: mesangial score, the presence or absence of glomeruloscloerosis, the presence or absence of endocapillary hypercellularity, and degree of tubular atrophy/interstitial fibrosis (MSET)

  3. Total number of glomeruli

  4. Number of glomeruli with endocapillary hypercellularity, extracapillary proliferation, global glomerulosclerosis, and segmental glomerulosclerosis

A. History Part I: Pattern Recognition:

The majority of patients with IgAN (40-50%) present with gross hematuria (possibly with flank/groin pain), that may follow an upper respiratory tract infection. These episodes may recur over the years.

Another large fraction of patients (30-40%) will present with microscopic hematuria with or without proteinuria that is incidentally noted on routine exam. Of these, one-fourth will proceed to develop gross hematuria in the upcoming years.

A small percentage (10%) of patients will present with frank nephrotic syndrome, rapidly progressive renal failure, or malignant hypertension. Acute kidney injury in these patients is usually triggered by one of three mechanisms with the following microscopic findings: 1) histological injury very similar to minimal change disease; 2) abundance of crescents (>50%) or segmental necrosis as may be seen in RPGN; or 3) tubular injury/obstruction caused by gross hematuria or damage by red cell lysis. While the latter is usually self-limiting and reversible over time, the first two usually require more urgent medical therapy.

B. History Part 2: Prevalence:

Since the etiology of IgA nephropathy is generally unknown, it is difficult to determine its predisposing factors. This disease is found mainly in Caucasions and Asians and rarely in African Americans. Although it can present at any age, it typically presents in the second and third decade of life. It has at least a 2:1 male to female predominance, with some studies showing up to 4:1 ratio. Although it is sometimes found with increasing frequency in certain families, there is no clear genomic inheritance pattern attributable to a single locus; rather it is thought to be a complex polygenic disease.

Furthermore, while most cases of IgAN are isolated to the kidney, it has been associated with certain systemic conditions that are known to increase IgA complex formation and deposition. This includes chronic liver disease (most common in EtOH cirrhosis, but also seen in hepatitis B, hepatitis C, and alpha 1 antitrypsin deficiency), celiac disease (33% of patients), and HIV. It is important to note that while mesangial IgA deposition may be seen in these conditions, this does not necessarily indicate active nephritis, and thus may not clinically be associated with IgAN.

IgAN has infrequently been associated with a variety of other diseases including dermatitis herpetiformis, Wegner's and other vasculities, seronegative arthritis (ankylosing spondylitis), small cell carcinoma, lymphoma, disseminated tuberculosis, bronchiolitis obliterans, and inflammatory bowel disease. The treatment of secondary IgAN is directed towards the underlying disease.

C. History Part 3: Competing diagnoses that can mimic IgA Nephritis.

Differential diagnosis for:

Persistent hematuria from a glomerular source (glomerular hematuria is characterized by the presence of red blood cell casts and/or dysmoprhic red blood cells on urinalysis):

  • Thin basement membrane nephropathy: generally benign, distinguished on renal biopsy with characteristic thinning of the glomerular basement membrane

  • Hereditary nephritis (Alport's Syndrome): X-linked autosomal dominant trait associated with sensorineural deafness, ophthalmologic abnormalities, and progressive renal failure

  • Primary or secondary proliferative glomerulonephritis (such as MSGN, membranous, FSGS)

Persistent hematuria from extra-glomerular source:

  • Renal parenchymal hematuria (renal cell carcinoma, tubulointerstitial disease (ATN, AIN), papillary necrosis, renal calculi)

  • Extra-renal parenchymal hematuria: Prostate cancer, benign prostatic hypertrophy

Differential diagnosis for IgA deposition on renal biopsy

  • Henoch-Schonlein purpura: systemic vasculitis characterized by palpable purpura, arthritis, and abdominal pain. Histologically identical to IgAN on renal biopsy (immunofluorescence microscopy demonstrating prominent globular deposits of IgA) thus distinguished by presence of other clinical features.

  • Lupus Nephritis: distinguished from IgAN by more prominent IgG deposition than IgA deposition, substantial C1q deposition (due to activation of classic complement pathway) rather than primarily C3.

D. Physical Examination Findings.

The clinical presentation of IgAN is variable. A majority of patients present with re-occurring episodes of gross hematuria, which may be associated with an infection, such as a viral URI. Patients with more severe or progressive disease generally present with hypertension, nephrotic syndrome (anasarca, hypertension, frothy urine), or clinical evidence of advanced kidney disease. As mentioned above, many patients will have silent disease and not present with any physical exam findings; the presence of microhematuria or proteinuria in these patients will be uncovered only on laboratory analysis.

E. What diagnostic tests should be performed?

IgAN is generally suspected based on clinical history (gross hematuria) and laboratory data (proteinuria, hematuria). It can be confirmed only on renal biopsy with histological evaluation and immunofluorescence presence of IgA deposits (gold standard).

Since the disease course of patients with IgAN who have isolated hematuria is generally benign, a renal biopsy is only recommended if there is evidence of more severe or progressive disease such as proteinurea > 0.5g/day, elevated serum creatinine or decreased GFR, or hypertension.

There are no known disease specific auto-antibodies. Plasma polymeric IgA1 levels are elevated in 30-50% of cases, although this is not specific enough to establish a diagnosis.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

1) Urinalysis with microscopy: evaluate for the presence of hematuria (should be done at more than one setting given low specificity of one isolated episode of hematuria).

2) Protein/creatinine ratio (or 24hour protein excretion): the degree of proteinuria is one of the strongest predictors of outcome and helps guide management. Proteinuria > 0.5g/day requires nephrology referral and initiation of supportive therapy. Persistent proteinuria may require additional treatment with steroids.

3) Serum creatinine and GFR to evaluate renal function: a downtrending creatinine clearance suggests progression of disease, in which case further treatment (steroids) should be considered. Of note, due to the indolent nature of disease, small decreases in GFR (estimated to be 1-3 ml/min per year) may not correlate with a rise in creatinine. In other words, a stable and normal creatinine may not indicate stable disease so one should also follow GFR trend. An already reduced GFR at the time of diagnosis portends a poorer prognosis.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

No imaging is required to make the diagnosis of IgA nephritis. A renal ultrasound may demonstrate features associated with chronic kidney disease (small size, increased echogenicity, cortical thinning) but is not specific to IgAN.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Approximately 10-15% of patients with IgAN who present with isolated hematuria (microscopic or macroscopic), insignificant or no proteinuria (<0.5g/24h), normal or near-normal renal function (GFR>50), and no hypertension will have spontaneous remission of disease. As such, in the absence of these features, the risks of a renal biopsy may outweigh the benefits.

III. Default Management.

There is no cure for IgAN. The goal of treatment is to stop or slow down disease progression. Evidence-based treatment guidelines are lacking due to poor quality studies with small sample size, sub-optimal methodologies (non-randomized, retrospective), and confounding variables yielding conflicting results. Furthermore, most comparison studies lack baseline optimization of supportive care, thus making it impossible to ascertain whether a particular treatment is beneficial above and beyond comprehensive supportive care.

Unfortunately, the KDIGOClinical Practice Guideline for Glomerulonephritis(to be published soon), will offer very few evidence-based recommendations and most will be suggestions based on opinion. An upcoming trial, STOP-IgAN, will assess if there are any additional benefits of immunosuppresive therapy in high risk patients who have already had optimal supportive therapy (expect results in 2014).

Management of IgAN primarily involves following clinical indicators of disease such as degree of proteinuria, blood pressure, and renal function (GFR) and the treatment is dependent upon patient risk (see below). The mainstay of treatment is to optimize supportive therapy for all patients at risk of or with evidence of disease progression (see below for details on recommended supportive therapy). In patients with more severe disease, immunosuppressive therapy with corticosteroids may be indicated.

Low risk patient:

  • Presents with microscopic or gross hematuria, no or minimal proteinuria (<0.5g), normal or near-normal GFR (>50 ml/min), and no hypertension

  • Management includes referral to nephrologist with yearly urine analysis, urine protein:creatinine ratio, GFR, and monitoring for development of hypertension

  • Studies demonstrate that 10-15% of patients with IgAN undergo spontaneous remission in the early stages. Conversely, approximately 30% will go on to have progressive disease

  • See below for management of patients with progressive disease

Moderate risk patient

  • Presents with persistant proteinuria (>0.5-1g/day) and/or reduced GFR (<50ml/min) and/or hypertension (>140/90)

  • If proteinuria > 0.5-1g/day but the GFR is greater 50ml/min, then a trial of only supportive therapy for 3-6 months is recommended (see below for details on recommended supportive therapy)

  • After 6months, If proteinuria is now < 0.5g/day and GFR decline is minimal (< 30%)and remains > 50ml/min, can continue supportive therapy alone

  • If proteinuria is increasing or persistently >0.5-1g/day and/or the GFR decline is greater than 30% despite supportive therapy (but remains >50ml/min), then consider initiation of corticosteroids as add-on therapy (seek nephrology consultation for regimen)

High risk patient

  • Presents with Acute Kidney Injury with rapid GFR loss with or without oliguria. May present with features of nephrotic syndrome or malignant hypertension. Of note, if there was significant gross hematuria, also consider non-glomerular causes of AKI that can be associated with IgAN, such as transient tubular obstruction and ATN (cause by red cell lysis). This is usually self-limiting and completely reversible in more than 75% of cases. Biopsy in these patients is only indicated if renal function does not improve within a few days.

  • In patients with AKI who present with features of nephrotic syndrome, which is more suggestive ofglomerular injury, a renal biopsy should be obtained immediately

  • Add immunosuppression such as corticosteroids once diagnosis is confirmed (seek immediate nephrology consultation)

  • Optimize supportive therapy (additive effects when used in conjuction with steroids)

Supportive therapy in IgAN

  • Angiotensin blockage: This is the first-line therapy for IgAN, especialy in those with proteinuria >0.5g/24hours and/or hypertension (BP >140/90). There is strong evidence that initiation of angiotension blockers (ACE-i or ARB) with titration to goal SBP < 120/80 and proteinuria <0.5g/24h can improve renal outcomes. There is not enough evidence to support combination ACEi/ARB therapy at this time. The general consensus is to avoid dihydropyridine calcium channel blockers.

  • Statins: Theoretically may have antiproliferative effects that can provide mesangial and glomerular protection independent of lipid control. Small studies have shown that statins may decrease proteinuria, however the effect on GFR is unclear. Furthermore, there is lacking evidence that statins have additional benefit when added to ACEi/ARB therapy. Consider statins in patients who may benefit from cardiovascular standpoint (lipid control) as CKD is known to be a CAD equivalent and should have the same LDL goals.

  • Fish oil: Theoretically may decrease platelet aggregation and inflammation mitigating glomerular injury. Small RCT trial from 2009 (30 patients) showed that combinition of fish oil and ACEi/ARB had greater reduction of proteinuria than ACEi/ARB monotherapy. Need larger RCT with long-term follow up to see effects on GFR and renal outcomes. Consider fish oil in patients who are able to tolerate the taste.

  • More generalized supportive therapy (for all CKD patients) include: restrict NaCL intake, control fluid intake, smoking cessation, avoiding NSAIDS, management of metabolic syndrome in obese patients, management of hyperphosphatemia, hyperparathyroidism, and metabolic acidosis, management of vitamin D deficiency if present, and protein restriction in advanced CKD patients

Immunosuppressive therapy

  • Corticosteroid therapy is the immunosuppressive therapy of choice for IgAN. While the precise regimen is yet to be determined, current recommendations based on the most recent studies (Mannoet al,2009 and Lvet al, 2009) are to start daily oral prednisone at a high dose (0.8-1.0mg/kg/day) and taper over 6-8months. Studies have not supported the use of alternating day or low dose regimen.

  • Other immunosuppressive agents such as Cyclophosphamide (cytoxan), Mycophenolate Mofetil (MMF), Cyclosporin, Azathioprine (imuran), etc, are not recommended in treatment of IgAN.

  • Immunosuppressive combinition therapy is also not recommended based on inconclusive results from available trials. Furthermore, adverse effects, such as hemorrhagic cystitis, PCP pneumonia, Tuberculosis, myelosuppresion, etc, are more common with combination therapy.

  • One exception for the use of combination therapy is in the rare case of a patient presenting with rapidly declining GFR (AKI) with renal biopsy showing crescentic and/or necrotizing IgAN, which share features of RPGN and/or vasculitis. In these patients, combination treatment with steroids and cyclophosphamide can be beneficial.

What to expect after treatment

While, large RCT analyzing long term renal outcomes and survival in IgAN patients treated with glucocorticoids are lacking, small studies (Manno et al, 2009 and Lv et al, 2009) suggest that treatment as outlined above slows the rate of GFR decline and thus progression to CKD. Furthermore, these studies suggest that the effects of 6-8month of glucocorticoid therapy is sustained beyond the initial treatment course.

Advanced disease with progression to CKD or ESRD

At present, there is not enough evidence to support immunosuppressive therapy (steroids) in advanced IgAN once serum creatinine > 2.5 and GFR < 30 (due to lack of trials in this population). In these patients, focus should be on optimizing supportive therapy with goal of slowing progression to ESRD.

In patients who have progressed to CKD stage V or ESRD, kidney transplantation (living donor or deceased donor) is an alternative option to Renal Replacement Therapy. Approximately 30% of patients will have recurrent disease in the transplanted kidney (especially if they had a rapid course with initial disease or if they were diagnosed at young age). It is important to note that while patients may have IgA deposition in the transplanted kidney, a majority will not have significant clinical disease and most patients will have good long-term graft survival (median of 10years). Therapy for recurrent IgAN after transplantation is only supportive (majority will already be on some form of immunosuppression) with the same agents as mentioned above.

Non-established treatment approaches

Anti-thrombotic agents include antiplatelet (ex: ASA or dipyridamole), anticoagulants (ex: warfarin with low INR goal), and thrombolytics (ex: urokinase). They are widely used in Southeast Asia for the management of IgAN. A recent meta-analysis of 6 RCTs totalling 320 patients (2011) demonstrated statistically significant effects on the reduction of proteinuria. However, the majority of studies did not have standarized use of ACEI/ARB for proteinuria. Furthermore, there was no effect on the GFR or renal survival.

Subgroup analysis showed that urokinase had both statistically signficant effects on the reduction of proteinuria as well as protection of renal function (in moderate to severe IgAN) with minimal increased risk of hyperkalemia and bleeding. Further studies with better methodology and longer follow- up are needed before anti-thrombotics can be reccommended as standard treatment for IgAN.

Tonsillectomy in combination with immunosuppression is routinely recommended in Japan based on two small non-randomized trials. No good quality study has been done to support tonsillectomy in other populations, thus the routine performance of this procedure in patients with IgAN is controversial and not currently recommended. However, one may consider tonsillectomy in patients who have a clear temporal relationship between tonsillitis and gross hematuria.

ETOH consumption (light to moderate) may be reno-protective in IgAN according to one study done in Finland (2009), independent of its effects on blood pressure and protein excretion. Need larger prospective RCT to further investigate before recommending this strategy.

A. Immediate management.

Immediate management is recommended in the small subset of patients who present with rapidly progressive glomerulonephritis or nephrotic syndrome. See management of the High Risk Patient above.

As in all patients with advanced CKD or ESRD, urgent dialysis may be required to manage severe volume or electrolyte abnormalities in patients with advanced IgAN

B. Physical Examination Tips to Guide Management.

The presence of elevated blood pressure, gross hematuria, anasarca, and oliguria are all concerning for ongoing disease or disease progression. While resolution of these suggest improvement, the disease can still progress silently in terms of non-nephrotic range proteinuria so the combination of physical exam and laboratory analysis should be used to guide management.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

1) Protein/creatinine ratio (or 24hour protein excretion): The degree of proteinuria is one of the strongest predictors of outcome and helps guide management. Proteinuria > 0.5g/day requires nephrology referral and initiation of supportive therapy. Persistent proteinuria may require additional treatment with steroids.

2) Serum creatinine and GFR to evaluate renal function. A downtrending creatinine clearance suggests progression of disease, in which case further treatment (steroids) should be considered. Of note, due to the indolent nature of disease, small decreases in GFR (estimated to be 1-3 ml/min per year) may not correlate with a rise in creatinine. In other words, a stable and normal creatinine may not indicate stable disease so one should also follow GFR trend.

D. Long-term management.

SeeSection III Default Management to review the supportive treatments that are recommended for long-term management IgAN and related CKD.

E. Common Pitfalls and Side-Effects of Management.

1) Monitor blood pressure, potassium and renal function when starting ACEi/ARB therapy.

2) Monitor glucose in patients on glucocorticoids.

3) Start Proton Pump Inhibitors for gastroprophylaxis in high risk patients who are on steroids (elderly, known history of peptic ulcer disease, concominant anti-platelet or anti-coagulation therapy, etc).

4) Consider PCP prophylaxis if a patient will be on long-term steroids.

5) Monitor bone health, optimize calcium and vitamin D, initiate bisphosphonate therapy in patients on long term steroids.

6) Monitor for infectious complications secondary to immunosuppressive therapy.

7) Monitor for non-infectious complications secondary to immunosuppressive therapy with steroids (cataracts, metabolic syndrome, etc).

IV. Management with Co-Morbidities.

A. Renal Insufficiency.

ACEi/ARB are still indicated as first line therapy in patients with CKD, unless contraindicated due to other factors such as hyperkalemia.

Immunosuppressive therapy is not recommended in patients with creatinine >2.5 and/or GFR<30ml/min.

B. Liver Insufficiency.

No change in standard management.

C. Systolic and Diastolic Heart Failure.

No change in standard management. ACEi/ARB therapy may have additional cardio-protective benefits in these patients.

D. Coronary Artery Disease or Peripheral Vascular Disease.

No change in standard management. Use antiplatelet, anticoagulation, fish oil, or statin therapy in patients who have clinical indications from cardiovascular perspective.

E. Diabetes or other Endocrine issues.

No change in standard management. Careful monitoring of blood glucose levels if corticosteroids are used. ACEi/ARB therapy may have additional cardio- and reno-protective benefits in patients with diabetes.

F. Malignancy.

No change in standard management. Since a majority of patients with IgAN will have a slowly progressive course, in cases of advanced malignancy, risks of treatment with immunosuppressive agents should be weighed against the less substantial benefits in this population with an overall poor long-term prognosis.

G. Immunosuppression (HIV, chronic steroids, etc).

No change in standard management. Monitor for increased risks of infections (including opportunistic and atypical) with corticosteroid use in patients already on other forms of immunosuppression and/or in immunocompromized patients.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management. Patients with COPD, asthma, or ILD may have other clinical indications for chronic steroids use. These patients should be closely monitored for infections (place on PCP prophylaxis) and for bone and metabolic complications of chronic steorids use.

I. Gastrointestinal or Nutrition Issues.

No change in standard management. Addition of Proton Pump Inhibitors for gastroprophylaxis in high risk patients who are started on steroids (elderly, known history of peptic ulcer disease, concomitant anti-platelet or anti-coagulation therapy, etc).

J. Hematologic or Coagulation Issues.

No change in standard management. Use antiplatelet or anticoagulation therapy in patients who have clinical indications for these agents. Monitor for bleeding side-effects.

K. Dementia or Psychiatric Illness/Treatment.

No change in standard management. Since a majority of patients with IgAN will have a slowly progressive course, in cases of advanced dementia or severe psychiatric illness, risks of treatment with immunosuppressive agents should be weighed against the less substantial benefits in this population with an overall poor long-term prognosis.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

Monitor for malignant hypertension and seek immediate nephrology consultation if this is present.

In patients who undergo renal biopsy, monitor for post-procedure complications such as bleeding.

B. Anticipated Length of Stay.

Patients with IgAN who have rapidly progressive disease or malignant hypertension or symptomatic gross hematuria may be hosptialized for immediate management for blood pressure control, renal biopsy, cyclophosphamide adjuvant therapy (to steroids), pain control, or rarely for urgent initiation of dialysis. In these patients, the anticipated length of stay is between 3-5days.

C. When is the Patient Ready for Discharge.

Discharge is usually considered safe if the blood pressure is stable (may not reach goal during the acute hospitalization) and renal function is stable.

D. Arranging for Clinic Follow-up.

1. When should clinic follow up be arranged and with whom.

Patients should have follow up with a Nephrologist within 1-4 weeks of discharge from the hospital depending on the severity of disease.

Patients should have follow up with their Primary Care Physician for non-kidney related side effects of steroid therapy and for routine health care.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

The following tests should be ordered prior to outpatient follow-up:

  • Urine analysis with microscopy, urine protein:creatinine ratio, and serum creatinine

  • If the patient was initiated on an ACEI or ARB, serum potassium and creatinine

  • If the patient presented with impaired renal function or have chronic kidney disease, PTH levels, serum calcium, serum phosphorus, serum potassium, vitamin D levels, and hemoglobin (to screen for anemia of chronic kidney disease)

E. Placement Considerations.

In the rare patient who presents with rapidly declining renal function due to IgAN that is not responding to initial management, renal replacement therapy with hemodialysis might be necessary. As such, close communication with nephrology regarding the time of RRT, the interventionalist for placement of vascular access, and the social worker for setting up outpatient HD centers will be important in expedited inpatient management.

F. Prognosis and Patient Counseling.

Patients who present with isolated hematuria in the absence of proteinuria, hypertension, or renal impairment have a 10-15% chance of spontaneous remission. Conversely, approximately 30% of patients will have a progressive disease course.

The degree of proteinuria is the strongest predictor of outcome in IgAN; higher proteinuria correlates with increased risk of renal failure and vice versa. Uncontrolled hypertension has an additive effect with proteinuria in driving progression of disease. In addition, renal prognosis is worse in patients who have a decreased GFR on presentation (at time of diagnosis) and in obese patients (likely due to superimposed obesity related renal changes). In those with progressive disease, ESRD will develop in about 15-20% of patients within 10 years and 30-40% within 20 years of diagnosis.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

None present. Can consider making the addition of ACEi/ARBs in patients with proteinuria >0.5mg/24h a core indicator.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

For patients receiving corticosteroid therapy, ensure proton pump inhibitor treatment is co-administered in high risk patients (elderly, known history of peptic ulcer disease, concomitant anti-platelet or anti-coagulation therapy, etc). These patients will also benefit from outpatient DEXA scan, calcium and vitamin D therapy in conjunction with a bisphosphanate for bone health. Finally, patients on chronic steroids should be started on PCP prophylaxis (Bactrim DS every Monday, Wednesday, Friday).

Ensure patient have adequate short term follow up with a Nephrologist and are able to make it to the appointment. In the case of patients initiated on hemodialysis, ensure they have the means to get to and from their designated dialysis centers.

VII. What's the evidence?

Jurgen, F, Eitner, F. "Current Therapy for IgA Nephropathy". J Am Soc Nephrology. vol. 22. 2011. pp. 1785-1794.

Cattran, D. "The Oxford Classification of IgA Nephropathy: Rationale, Clinicopathological Correlations, and Classification?". Kidney International. vol. 76. 2009. pp. 534-545.

Liu, XJ. "Antithrombotic Drug Therapy for IgA Nephropathy: A Meta Analysis of Randomized Controlled Trials". Intern Medicine. vol. 50. 2011. pp. 2503-2510.

Barratt, J, Feehally, J. "IgA Nephropathy". J Am Soc Nephrology. vol. 66. 2005. pp. 905.

"Treatment of IgA Nephropathy: An Update". Ann of Pharmacother. vol. 45. 2011. pp. 1284-1296.

Ponticelli, C, Glassock, RJ. "Posttransplant recurrence of primary glomerulonephritis". J Am Soc Nephrol. vol. 12. 2010. pp. 2362-2372.

Lv, J. "Combination therapy of prednisone and ACE inhibitor verus ACE inhibitor therapy alone in patients with IgA nephropathy: A randomized controlled trial". Am J Kidney Dis. vol. 53. 2009. pp. 26-32.

Pozzi, C. "Corticosteroids in IgA nephropathy: a randomised controlled trial". Lancet. vol. 353. 1999. pp. 883-887.

Pozzi, C. "Corticosteroid effectiveness in IgA nephropathy: Long-term results of a randomized, controlled trial". J AmSoc Nephrol. vol. 15. 2004. pp. 157-163.

Manno, C. "Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow up in proteinuric IgA nephropathy". Nephrol Dial Transplant. vol. 24. 2009. pp. 3694-3707.

You must be a registered member of Clinical Advisor to post a comment.
close

Next Article in Hospital Medicine

Sign Up for Free e-newsletters