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__NOTOC__
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{{IgA nephropathy  }}
{{IgA nephropathy  }}
{{CMG}}
{{CMG}}; {{AE}}{{OO}}, {{APM}}
==Overview==
==Medical Therapy==
The ideal treatment for IgAN would remove IgA from the glomerulus and prevent further IgA deposition.  This goal still remains a remote prospect. There are a few additional caveats that have to be considered while treating IgA nephropathy. IgA nephropathy has a very variable course, ranging from a benign recurrent [[hematuria]] up to a rapid progression to [[chronic renal failure]]. Hence the decision on which patients to treat should be based on the prognostic factors and the risk of progression. Also, IgA nephropathy recurs in [[transplant]]s despite the use of [[ciclosporin]], [[azathioprine]] or [[mycophenolate mofetil]] and [[steroid]]s in these patients. There are persisting uncertainties, due to the limited number of patients included in the few controlled randomized studies performed to date, which hardly produce statistically significant evidence regarding the heterogeneity of IgA nephropathy patients, the diversity of study treatment protocols, and the length of follow-up.


Patients with isolated hematuria, [[proteinuria]] < 1 g/day and normal [[renal function]] have a benign course and are generally just followed up annually. In cases where [[tonsillitis]] is the precipitating factor for episodic hematuria, [[tonsillectomy]] has been claimed to reduce the frequency of those episodes. However, it does not reduce the incidence of progressive [[chronic renal failure|renal failure]]{{ref|Xie}}. Also, the natural history of the disease is such that episodes of frank [[hematuria]] reduce over time, independent of any specific treatment. Similarly, [[prophylactic]] [[antibiotic]]s have not been proven to be beneficial.  Dietary [[gluten]] restriction, used to reduce mucosal [[antigen]] challenge, also has not been shown to preserve [[renal function]]. [[Phenytoin]] has been also been tried without any benefit{{ref|Clarkson}}.<ref name="pmid15086452">{{cite journal| author=Xie Y, Chen X, Nishi S, Narita I, Gejyo F| title=Relationship between tonsils and IgA nephropathy as well as indications of tonsillectomy. | journal=Kidney Int | year= 2004 | volume= 65 | issue= 4 | pages= 1135-44 | pmid=15086452 | doi=10.1111/j.1523-1755.2004.00486.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15086452  }} </ref> <ref name="pmid6994960">{{cite journal| author=Clarkson AR, Seymour AE, Woodroffe AJ, McKenzie PE, Chan YL, Wootton AM| title=Controlled trial of phenytoin therapy in IgA nephropathy. | journal=Clin Nephrol | year= 1980 | volume= 13 | issue= 5 | pages= 215-8 | pmid=6994960 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6994960  }} </ref>
==[[IgA nephropathy|Medical Therapy]]==
According to “The National Kidney Foundation: Kidney Disease - Improving Global Outcomes” (NKF-KDIGO)<ref name="pmid15882273">{{cite journal| author=Haubitz M, Wittke S, Weissinger EM, Walden M, Rupprecht HD, Floege J et al.| title=Urine protein patterns can serve as diagnostic tools in patients with IgA nephropathy. | journal=Kidney Int | year= 2005 | volume= 67 | issue= 6 | pages= 2313-20 | pmid=15882273 | doi=10.1111/j.1523-1755.2005.00335.x | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15882273 }} </ref> in 2012, the management and treatment recommendations of primary IgA nephropathy are as follows:


A subset of IgA nephropathy patients, who have [[minimal change disease]] on light [[microscopy]] and clinically have [[nephrotic syndrome]], show an exquisite response to [[steroid]]s, behaving more or less like [[minimal change disease]]. In other patients, the evidence for steroids is not compelling.  Short courses of high dose steroids have been proven to lack benefit.  However, in patients with preserved [[renal function]] and proteinuria (1-3.5 g/day), a recent prospective study has shown that 6 months regimen of steroids may lessen proteinuria and preserve renal function{{ref|Kobayashi}}. However, the risks of long-term steroid use have to be weighed in such cases.  It should be noted that the study had 10 years of patient follow-up data, and did show a benefit for steroid therapy; there was a lower chance of reaching end-stage renal disease (renal function so poor that dialysis was required) in the steroid group.  Importantly, angiotensin-converting enzyme inhibitors were used in both groups equally.
===Goals of Management===


[[Cyclophosphamide]] had been used in combination with antiplatelets / [[anticoagulant]]s in unselected IgA nephropathy patients with conflicting results. Also, the side effect profile of this drug, including long term risk of [[malignancy]] and [[infertility|sterility]], made it an unfavorable choice for use in young adults. However, one recent study, in a carefully selected high risk population of patients with declining GFR, showed that a combination of steroids and [[cyclophosphamide]] for the initial 3 months followed by [[azathioprine]] for a minimum of 2 years resulted in a significant preservation of renal function {{ref|Ballardie}}. Other agents such as [[mycophenolate mofetil]], [[ciclosporin]] and mizoribine have also been tried with varying results.
*Prevent the occurrence of repeated episodes of [[AKI]] and persistent [[Hematuria|macroscopic hematuria]]<ref name="pmid22895519">{{cite journal| author=Radhakrishnan J, Cattran DC| title=The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. | journal=Kidney Int | year= 2012 | volume= 82 | issue= 8 | pages= 840-56 | pmid=22895519 | doi=10.1038/ki.2012.280 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22895519 }} </ref>
*Reduce [[proteinuria]] to less than 1 g/24 hrs in adults and to less than 0.5 g/24 hrs in children regardless of baseline [[proteinuria]] at diagnosis<ref name="pmid22895519">{{cite journal| author=Radhakrishnan J, Cattran DC| title=The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. | journal=Kidney Int | year= 2012 | volume= 82 | issue= 8 | pages= 840-56 | pmid=22895519 | doi=10.1038/ki.2012.280 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22895519 }} </ref><ref name="pmid17978307">{{cite journal| author=Reich HN, Troyanov S, Scholey JW, Cattran DC, Toronto Glomerulonephritis Registry| title=Remission of proteinuria improves prognosis in IgA nephropathy. | journal=J Am Soc Nephrol | year= 2007 | volume= 18 | issue= 12 | pages= 3177-83 | pmid=17978307 | doi=10.1681/ASN.2007050526 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17978307 }} </ref>
A study from Mayo Clinic did show that long term treatment with omega-3 fatty acids results in reduction of progression to [[renal failure]], without, however, reducing [[proteinuria]] in a subset of patients with high risk of worsening [[kidney function]]{{ref|Donadio}}. However, these results have not been reproduced by other study groups and in two subsequent meta-analyses {{ref|Strippoli}}{{ref|Dillon}}. However, fish oil therapy does not have the drawbacks of [[immunosuppressive therapy]]. Also, apart from its unpleasant taste and abdominal discomfort, it is relatively safe to consume.  
*Control [[blood pressure]] to < 130/80 mmHg if [[proteinuria]] is > 0.3 g/24 hrs and more aggressively to <125/75 mmHg if [[proteinuria]] is 1g/24 hrs<ref name="pmid22895519">{{cite journal| author=Radhakrishnan J, Cattran DC| title=The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. | journal=Kidney Int | year= 2012 | volume= 82 | issue= 8 | pages= 840-56 | pmid=22895519 | doi=10.1038/ki.2012.280 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22895519 }} </ref>
*Reduce avoidable risk factors, such as [[obesity]]. [[Weight loss]] to a [[BMI]]<25 kg/m2 is recommended to patients with IgA nephropathy to reduce obesity and cardiovascular co-morbidities and degree of proteinuria<ref name="pmid22895519">{{cite journal| author=Radhakrishnan J, Cattran DC| title=The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. | journal=Kidney Int | year= 2012 | volume= 82 | issue= 8 | pages= 840-56 | pmid=22895519 | doi=10.1038/ki.2012.280 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22895519 }} </ref>


The events that tend to progressive renal failure are not unique to IgA nephropathy and non-specific measures to reduce the same would be equally useful. These include low-protein diet and optimal control of [[blood pressure]]. The choice of the [[antihypertensive]] agent is open as long as the blood pressure is controlled to desired level. However, [[Angiotensin converting enzyme inhibitor]]s and [[Angiotensin II receptor antagonist]]s are favoured due to their anti-proteinuric effect.
===Treatment===
 
====Supportive Measures====
 
Supportive measures are to performed in IgA nephropathy similar to the measures required for management of [[Acute tubular necrosis|ATN]]<ref name="pmid22895519">{{cite journal| author=Radhakrishnan J, Cattran DC| title=The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. | journal=Kidney Int | year= 2012 | volume= 82 | issue= 8 | pages= 840-56 | pmid=22895519 | doi=10.1038/ki.2012.280 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22895519 }} </ref>
 
*Indication: Remarkable presence of only [[ATN]] and intratubular [[RBC casts]]
 
====Pharmacologic Therapy====
*'''[[Angiotensin-converting enzyme inhibitor|Angiotensin-converting enzyme inhibitor (ACE-I)]] or [[Angiotensin II receptor antagonist|angiotensin II-receptor blocker (ARB)]]'''<ref name="pmid22895519">{{cite journal|author=Radhakrishnan J, Cattran DC| title=The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. | journal=Kidney Int| year= 2012 | volume= 82 | issue= 8 | pages= 840-56 | pmid=22895519 | doi=10.1038/ki.2012.280| pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22895519 }} </ref>
** To titrate dosages as required and as tolerated<ref name="pmid22895519">{{cite journal| author=Radhakrishnan J, Cattran DC| title=The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. | journal=Kidney Int | year= 2012 | volume= 82 | issue= 8 | pages= 840-56 | pmid=22895519 | doi=10.1038/ki.2012.280 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22895519 }} </ref>
**Duration: Chronic
**Indications:
***[[Proteinuria]] > 1g/24 hrs in adults or 0.5 g/24 hrs in children
***[[Blood pressure]] > 130/80 mmHg if proteinuria < 1g/24 hrs
***[[Blood pressure]] > 125/75 mm Hg if proteinuria > 1g/24 hrs
 
[[ACE-I]] or [[ARB]] are helpful to reduce [[proteinuria]]. Nonetheless, [[Randomized controlled trial|randomized clinical trials (RCT)]] have not yet been conducted to assess their role in reducing the progression to [[ESRD]]. Although combination therapy has been proven more effective in monotherapy in some studies<ref name="pmid10213639">{{cite journal| author=Russo D, Pisani A, Balletta MM, De Nicola L, Savino FA, Andreucci M et al.| title=Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy. | journal=Am J Kidney Dis | year= 1999 | volume= 33 | issue= 5 | pages= 851-6 | pmid=10213639 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10213639 }} </ref><ref name="pmid16047643">{{cite journal| author=Yang Y, Ohta K, Shimizu M, Nakai A, Kasahara Y, Yachie A et al.| title=Treatment with low-dose angiotensin-converting enzyme inhibitor (ACEI) plus angiotensin II receptor blocker (ARB) in pediatric patients with IgA nephropathy. | journal=Clin Nephrol | year= 2005 | volume= 64 | issue= 1 | pages= 35-40 | pmid=16047643 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16047643 }} </ref>, [[KDIGO guidelines classification scheme|KDIGO guidelines]] have not made recommendations about combination therapy yet pending RCTs.
 
*'''[[Corticosteroids]]'''<ref name="pmid22895519">{{cite journal|author=Radhakrishnan J, Cattran DC| title=The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. | journal=Kidney Int| year= 2012 | volume= 82 | issue= 8 | pages= 840-56 | pmid=22895519 | doi=10.1038/ki.2012.280| pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22895519 }} </ref>
**Duration: 6 months
**Indication: [[GFR]] > 50 ml/min/1.73m2 and [[Proteinuria|persistent proteinuria]] > 1g/24 hrs despite [[ACE-I]] or [[ARB]] and BP control
 
The use of [[steroids]] in patient with a [[GFR]]<50 ml/min/1.73m2 has not been studied yet. Specific dosage is not yet recommended according to [[KDIGO guidelines classification scheme|KDIGO guidelines]]. There are more observed side-effects with high-dose pulse [[corticosteroids]].
 
*'''[[Immunosuppressive agents]]''' (''[[cyclophosphamide]], [[azathioprine]]'')<ref name="pmid22895519">{{cite journal|author=Radhakrishnan J, Cattran DC| title=The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. | journal=Kidney Int| year= 2012 |volume= 82 | issue= 8 | pages= 840-56 | pmid=22895519 | doi=10.1038/ki.2012.280| pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22895519 }} </ref>
**Duration: [[Cyclophosphamide]]: 3 months and [[azathioprine]]: minimum 2 years.
**Indication: Patients on [[steroid]] therapy with rapidly progressive IgA nephropathy and >50% crescent formation on biopsy
 
[[Immunosuppressive agents]] should not be used in patients with low [[GFR]] < 30 ml/min/1.73m2 except if indicated as above. The dose of [[steroid]] must be reduced when using concomitant [[Immunosuppressive therapy|immunosuppressive therapy.]] One RCT showed better [[kidney function]] by reducing [[corticosteroid]] dose from 40mg/d to 10mg/d with use of [[cyclophosphamide]] at 1.5mg/kg/d for 3 months followed by [[azathioprine]] at 1.5mg/kg/d for at least 2 years.
 
*'''[[Fish oil]]'''<ref name="pmid22895519">{{cite journal|author=Radhakrishnan J, Cattran DC| title=The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. | journal=Kidney Int| year= 2012 |volume= 82 | issue= 8 | pages= 840-56 |pmid=22895519 | doi=10.1038/ki.2012.280| pmc=|url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22895519 }} </ref>
**Indication: Persistent [[proteinuria]] > 1g/24 hrs despite 3-6 months of optimal [[ACE-I]] or [[ARB]] and blood pressure control.
 
Fish oil at a dose of 12g/d was shown to improve renal outcome in patients with IgA nephropathy in trials by reducing rate of [[ESRD]] in 4 years from 40% to only 4%.<ref name="pmid7935657">{{cite journal| author=Donadio JV, Bergstralh EJ, Offord KP, Spencer DC, Holley KE| title=A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group. | journal=N Engl J Med | year= 1994 | volume= 331 | issue= 18 | pages= 1194-9 | pmid=7935657 | doi=10.1056/NEJM199411033311804 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7935657 }} </ref> In another 6-month study, 3g/d dose also showed better prognosis with less [[proteinuria]].<ref name="pmid10446945">{{cite journal| author=Donadio JV, Grande JP, Bergstralh EJ, Dart RA, Larson TS, Spencer DC| title=The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. Mayo Nephrology Collaborative Group. | journal=J Am Soc Nephrol | year= 1999 | volume= 10 | issue= 8 | pages= 1772-7 | pmid=10446945 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10446945 }} </ref>


==References==
==References==
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[[Category:Nephrology]]
[[Category:Nephrology]]
[[Category:Genetic disorders]]
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Latest revision as of 12:54, 20 July 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Olufunmilola Olubukola M.D.[2], Ali Poyan Mehr, M.D. [3]

Medical Therapy

According to “The National Kidney Foundation: Kidney Disease - Improving Global Outcomes” (NKF-KDIGO)[1] in 2012, the management and treatment recommendations of primary IgA nephropathy are as follows:

Goals of Management

Treatment

Supportive Measures

Supportive measures are to performed in IgA nephropathy similar to the measures required for management of ATN[2]

  • Indication: Remarkable presence of only ATN and intratubular RBC casts

Pharmacologic Therapy

ACE-I or ARB are helpful to reduce proteinuria. Nonetheless, randomized clinical trials (RCT) have not yet been conducted to assess their role in reducing the progression to ESRD. Although combination therapy has been proven more effective in monotherapy in some studies[4][5], KDIGO guidelines have not made recommendations about combination therapy yet pending RCTs.

The use of steroids in patient with a GFR<50 ml/min/1.73m2 has not been studied yet. Specific dosage is not yet recommended according to KDIGO guidelines. There are more observed side-effects with high-dose pulse corticosteroids.

Immunosuppressive agents should not be used in patients with low GFR < 30 ml/min/1.73m2 except if indicated as above. The dose of steroid must be reduced when using concomitant immunosuppressive therapy. One RCT showed better kidney function by reducing corticosteroid dose from 40mg/d to 10mg/d with use of cyclophosphamide at 1.5mg/kg/d for 3 months followed by azathioprine at 1.5mg/kg/d for at least 2 years.

Fish oil at a dose of 12g/d was shown to improve renal outcome in patients with IgA nephropathy in trials by reducing rate of ESRD in 4 years from 40% to only 4%.[6] In another 6-month study, 3g/d dose also showed better prognosis with less proteinuria.[7]

References

  1. ↑ Haubitz M, Wittke S, Weissinger EM, Walden M, Rupprecht HD, Floege J; et al. (2005). "Urine protein patterns can serve as diagnostic tools in patients with IgA nephropathy". Kidney Int. 67 (6): 2313–20. doi:10.1111/j.1523-1755.2005.00335.x. PMID 15882273.
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 Radhakrishnan J, Cattran DC (2012). "The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient". Kidney Int. 82 (8): 840–56. doi:10.1038/ki.2012.280. PMID 22895519.
  3. ↑ Reich HN, Troyanov S, Scholey JW, Cattran DC, Toronto Glomerulonephritis Registry (2007). "Remission of proteinuria improves prognosis in IgA nephropathy". J Am Soc Nephrol. 18 (12): 3177–83. doi:10.1681/ASN.2007050526. PMID 17978307.
  4. ↑ Russo D, Pisani A, Balletta MM, De Nicola L, Savino FA, Andreucci M; et al. (1999). "Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy". Am J Kidney Dis. 33 (5): 851–6. PMID 10213639.
  5. ↑ Yang Y, Ohta K, Shimizu M, Nakai A, Kasahara Y, Yachie A; et al. (2005). "Treatment with low-dose angiotensin-converting enzyme inhibitor (ACEI) plus angiotensin II receptor blocker (ARB) in pediatric patients with IgA nephropathy". Clin Nephrol. 64 (1): 35–40. PMID 16047643.
  6. ↑ Donadio JV, Bergstralh EJ, Offord KP, Spencer DC, Holley KE (1994). "A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group". N Engl J Med. 331 (18): 1194–9. doi:10.1056/NEJM199411033311804. PMID 7935657.
  7. ↑ Donadio JV, Grande JP, Bergstralh EJ, Dart RA, Larson TS, Spencer DC (1999). "The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. Mayo Nephrology Collaborative Group". J Am Soc Nephrol. 10 (8): 1772–7. PMID 10446945.

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